Abstract Objectives This study looked at how Cucumeropsis mannii seed oil (CMSO) affected male Wistar albino rats’ liver damage caused by bisphenol A (BPA). Methods The standard HPLC method was used to assess the CMSO’s phenolic content. Then, six (n = 8) groups of 48 male Wistar rats (150 20 g) each received either CMSO or olive oil before being exposed to BPA for 42 days. Groups: A (1 ml of olive oil, regardless of weight), B (BPA 100 mg/kg body weight (BW)), C (CMSO 7.5 mg/kg BW), D (CMSO 7.5 mg/kg BW + BPA 100 mg/kg BW), E (CMSO 5.0 mg/kg BW + BPA 100 mg/kg BW), and F (CMSO 2.5 mg/kg BW + BPA 100 mg/kg BW). Key findings A surprising abundance of flavonoids, totalling 17.8006 10.95 g/100 g, were found in the HPLC data. Malondialdehyde, liver enzymes, reactive oxygen species, total bilirubin, and direct bilirubin levels were all significantly elevated by BPA (P = 0.05). Additionally, nuclear factor-B, interleukin-6, interleukin-1, tumour necrosis factor, and histological alterations were all considerably (P = 0.05) caused by BPA. The altered biochemical markers and histology were, however, noticeably recovered by CMSO to a level that was comparable to the control. Conclusions Due to the abundance of flavonoid components in the oil, CMSO protects the liver from BPA-induced hepatotoxicity by lowering oxidative stress and inflammatory reactions.