Caesalpinia bonduc and C. decapeleta var. japonica have great importance in traditional medicine systems but scientific information’s are still lacking for their potentials. To explore their bioactivity, we assessed the antioxidant, enzyme inhibitory abilities of the dichloromethane (DCM), ethyl acetate, methanol, and water extracts prepared from the leaves and bark. The cytotoxicity and anticancer properties of the extracts were also assessed in vitro. The water extract of C. decapeleta leaves possessed highest phenolic content (108.16 mg gallic acid equivalent (GAE)/g extract), while the highest flavonoid content was recorded for the C. bonduc leaf methanolic extract (27.89 mg rutin equivalent (RE)/g extract). In general, C. decapeleta extracts possessed higher radical scavenging potential compared to C. bonduc extracts. C. decapeleta DCM leaves extract (10.20 mg galantamine equivalent (GALAE)/g extract) showed highest inhibition against butyrylcholinesterase. The cytotoxicity of the most potent methanolic and aqueous extracts were assessed against four cell lines. The chemical profiles of both species appeared to be different. C. bonduc was abundant in organic and phenolic acids as well as their esters. Flavonoid glycosides, bonducellin and its derivatives and caesalminaxins were identified. Whereas, C. decalpetala possessed many galloylated compounds. The cytotoxicity of C. bonduc and C. decapetala extracts was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based assay on VERO (kidney of an adult African Green monkey cells), HeLa (human cervical adenocarcinoma cells), RKO (human colon carcinoma cells), FaDu (human hypopharyngeal squamous carcinoma cells) cell lines. C. bonduc bark water extract exhibited the highest cytotoxicity towards HeLa (50 % cytotoxic concentration (CC50): 28.5 μg/mL) cancer cell line, as compared to normal VERO cells (CC50:35.87 μg/mL). For C. decapetala, the highest cytotoxicity was found for bark methanol extract on the HeLa cells with CC50 of 46.08 μg/mL and selectivity index of 3.33. In the gene ontology analysis, prostate cancer, nuclear factor kappa B (NF-kappa B) signaling, proteoglycans in cancer pathways might support the results of the cytotoxic assays. These results showed that the tested Caesalpinia species, showing potent inhibitory action against butyrylcholinesterase, might represent novel phytotherapeutic avenues for the management of Alzheimer’s disease.