Museo De La Salle is patterned after some of the best examples of the bahay na bato in the Philippines, especially the Constantino house in Balagtas, Bulacan; the Arnedo-Gonzales house in Sulipan, Apalit, Pampanga; and the Santos-Joven-Panlilio house in Bacolor, Pampanga.

The building itself takes design inspiration from the 19th century bahay na bato, a two-storey building with stone, brick and mortar structure at the ground level, and usually a wood one at the second level. The emergence of the bahay na bato marked the remarkable lifestyle of the 19th century Christian Philippines. A bahay na bato was filled with fine furniture and objects to showcase the owner's wealth, personal style, and status in society. These examples of material culture now serve to document a range of natural and socio-historical notions.

Outside
The tile-roofed structure is walled with adobe, which keeps the ground floor interiors cool. The fachada or façade is typical of the era, with wide tall doors; iron grilles for ground-floor windows; and details such as ventanillas lined with balustres de torno, bandejas, and molduras or mouldings.

At the back of the Museo, accessed from the azotea stairs, is the jardin or garden, which is mostly planted to traditional turn-of-the-century botanical species, such as the champaca, cadena de amor, campanilla, sampaguita, dama de noche, adelfa, and ylang-ylang, as well as different kinds of gumamela.

A fountain and sculptural works executed by the atelier in Quiapo,
Manila, of the 19th century Philippine master carver-sculptor Isabelo Tampingco, and granite benches round up the garden layout.

Inside
The arched puerta mayor or main door, which is opened only for the exit and entrance of carriages and carrozas, is made of balayong. A postigo or door for pedestrians is cut into the puerta mayor.

Interior design details of the caida, sala mayor, despacho, cuarto, oratorio, comedor, and cocina such as color, woodwork, and interior handpainting were guided by extensive research, particularly into pertinent styles during the Spanish Colonial Period from the 1850s through the late 1880s, and Philippine art nouveau in the late 1890s to the early American Colonial Period.

Zaguan
The Zaguan, from an Arabic term meaning "passageway", is the ground floor space of the house, normally having several rooms which served as storage for carrozas, grain harvest, and old furniture. A huge Puerta Mayor (main door) with smaller postigos (pedestrian doors) leads guests into the zaguan. The rooms in the zaguan now function as offices, and the lobby as venue for lectures, conferences, and performances.

Caida
The foyer or caida (from the Spanish word "caer" meaning to drop or to let fall) is the traditional receiving area, where women would let fall of the hemlines and trains of their saya (long skirts), which they clip as they navigate the staircase. The caida is a drawing room for entertaining friends on ordinary occasions, so spacious also as to serve as an all-in-one room where the family could, likewise, dine, saw, and sometimes dance. The area highlights the 1880 architectural design. The ceiling is made of pressed metal sheets in aqua and red to blend with the handpaintings on the walls.

Sala Mayor
The Sala Mayor is a place for parties known as tertulias. It has the color of the Spanish flag, the Bandera Española red and yellow and was lavishly done in the late 1880s style. Its decoration takes influence from the Spanish ayuntamiento or city hall. The walls and ceilings are hand-painted in traditional Spanish Victorian motif. The doors are in solid bandejas and draped with heavy Italian damask curtains accented by European tassels. The chairs and tables were made of light materials that can be moved to the sides during tertulias.

Planks of the local hardwoods balayong and narra compose the woodworks which cannot be pierced by ordinary nails. Pegs, dowels, and tongue-and-groove were used to secure the wood in place.

Also in the sala are 19th century oil portraits of Don Jose Leon Santos (dated 1887) and Doña Ramona Joven (dated 1882) by Simon Flores y Dela Rosa, a miniaturist and portrait artist. Simon Flores who studied at the Academia De Dibujo y Pintura, was the first Filipino of native blood, to win a prize from an international competition.

Comedor
Large and well-furnished as the sala mayor is the comedor. Crystal chandeliers hung low from the ceiling over the dining table while aparadores for the crystal, silver and chinaware stand against the walls. Punkahs or ceiling cloth fans hung low at both sides of the chandelier, which a servant used to pull with a long cord as her masters were dining-in.

Cocina
The cocina is sometimes a separate structure from the house because it is considered a fire hazard. It is connected to the house by a causeway. The cocina is an area for activities such as cooking, grain pounding and clothes ironing. It features a pugon or hurno (oven) with a shape of an igloo, operated using firewood. The banggerahan, the traditional dish dryer, contains porcelain plates and drinking glasses showing how this feature was traditionally used.

Clothes ironing were also done in the cocina, thus earlier forms of flat iron were featured. One example is the prensa de piye which lies on the floor. A prensa de piye is a wooden press which uses ones feet in pressing the clothes.

Azotea
Aside from being a place for washing and drying clothes, the ever-romantic azotea, with its arched stone supports, is a hanging garden and a recreation area where one could have tea in the afternoons. A cistern called aljibe is located at one side. On rainy days, water coming from the roof of the house is filtered then collected in the aljibe.

Kitchen stairs and jardin
Kitchen stairs were back entrances paved with piedra China (Chinese granite). The stairs lead to the jardin which showcases turn-of-the-century plants. Gumamela of different varieties, champaca, cadena de amor, bandera española, sampaguita, dama de noche, adelfa and ilang-ilang give the surrounding a fresh provincial aura. A fountain executed by the artist Isabelo Tampinco and granite benches rest on the jardin.