The chemical study of hydroethanolic extracts from different parts of Trichilia prieuriana (Meliaceae) led to the isolation and identification of 22 compounds: 2 β ,3 β ,4 β -trihydroxypregnan-16-one ( 1 ), prieurianin ( 2 ), flindissone ( 3 ), deoxyflindissone ( 4 ), picraquassin E ( 5 ), ursolic acid ( 6 ), 3 β -acetoxy-11 α -hydroxyurs-12-en ( 7 ), 3 β -acetoxy-urs-12-en-11-one ( 8 ), 3 β -acetoxy- β -amyrin ( 9 ), friedelin-3-ol ( 10 ), 3-oxo, friedelin ( 11 ), 3-oxo, fridelin-28-ol ( 12 ), oleanolic acid ( 13 ), hederagenin ( 14 ), mixture of stigmasterol ( 15 ), β -sitosterol ( 16 ), β -sitosterol-3- O - β -glucopyranoside ( 17 ) and stigmasterol-3- O - β -glucopyranoside ( 18 ), erythrodiol ( 19 ), scopoletin ( 20 ), 4-hydroxy-3,5-dimethoxybenzoic acid ( 21 ) and shikimic acid ( 22 ). The absolute configurations and crystal structures of compounds 1 and 2 are reported herein for the first time. Crude extracts, fractions and isolated compounds were evaluated for their antibacterial activities against nine bacterial strains. Crude extracts from the root wood of T. prieuriana exhibited good antibacterial potency with minimal inhibitory concentration (MIC) values ranging from 31.25 to 500 µg mL −1 on the test bacteria. The ethyl acetate fraction from root wood and n -hexane-ethyl acetate (3:1) fraction from leaves showed a moderate antibacterial activity with MIC value of 250 μg mL −1 on all test bacteria. Isolated compounds exhibited significant antibacterial activity with MIC values ranging from 4.09 to 71.8 µ m . Compounds 3 , 6 and 7 were the most active with a broad spectrum of activities.