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Background: Attention has recently focused on mitochondrial-mediated apoptosis as a signaling pathway that is disrupted in many diseases involving excessive cell proliferation. Medicinal plants that induce apoptosis may be useful in chemoprevention. Cajanus cajan (C. cajan) is cultivated in East and West Africa. It is used in folk medicine for the treatment of liver injury, anemia, dysentery, measles, jaundice, and tumor. Purpose: This study aims to investigate the in vitro antioxidant and mitochondrial-mediated apoptotic effects of C. cajan. Methods: The mitochondrial permeability transition (mPT), mitochondrial ATPase activity, (2, 2-diphenylpicrylhydrazyl) DPPH radical-scavenging activity, total antioxidant capacity, and total phenol and apoptotic biomarkers were assessed while the phytochemicals present in the extract were determined by gas chromatography-mass spectrometry (GC–MS). Methanol extract of Cajanus cajan (MECC) triggered mitochondrial-mediated apoptosis by induction of pore opening, enhancement of mitochondrial ATPase activities, and increased immunohistochemical expression of caspase 3, caspase 9, and cytochrome c. Results: MECC triggered mitochondrial-mediated apoptosis by induction of pore opening and increased expression of caspase 3, caspase 9, and cytochrome c. Enhancement of ATPase activities inhibition of lipid peroxidation and DPPH scavenging activity of DPPH were observed. Conclusions: These findings suggest that C. cajan-induced mitochondrial-mediated apoptosis in normal rat liver through the induction of mPT and eventual release of cytochrome c which is a prelude to the progression of apoptosis. Hence, certain bioactive components of C. cajan may be useful in chemoprevention and management of conditions associated with insufficient apoptosis. [ABSTRACT FROM AUTHOR]