Eight new limonoids, khayseneganins A-H (1-8), and 31 known limonoids were isolated from the leaves and twigs of Khaya senegalensis. The structures of the new compounds were elucidated by 2D-NMR spectroscopy and mass spectrometry, and the absolute configuration of 1 was determined by the CD exciton chirality method. Compounds 9, 10, 12, and 15 showed antimicrobial activities against Pseudomonas aeruginosa, MRSA 92(#), and MRSA 98(#), all with a MIC value of 12.5 μg/mL.