Diclofenac administration has been associated with several health problems in human including gastrointestinal tract problems, renal toxicity, among others. Several medicinal plants are been used locally for the treatment of several diseases. The aim of this study was to investigate the potential of fermented unripe plantain juice (FUPJ) in ameliorating diclofenac-induced ulcer and renal dysfunction. Twenty (20) healthy adult Wister rats weighing between 110g to 200g were randomly divided into four groups of five rats each. Group I served as control, received distilled water and feeds, Group 2 received 10mg/kg body weight of diclofenac only, Group 3 received 10mg/kg body weight of diclofenac only and post treated with 200mg/kg body weight of FUPJ and Group 4 received 200mg/kg body weight of FUPJ. The diclofenac was administered IP and fermented unripe plantain extract was administered orally for fourteen (14) days. The results showed that diclofenac administration caused a significant increase (p<0.05) in serum levels of creatinine and a significant decrease (p<0.05) in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) compared to the control group. Additionally, diclofenac administration caused ulceration in the gastric mucosa. However, treatment with FUPJ significantly reduced (p<0.05) the levels of creatinine, urea, and MDA and increased (p<0.05) the levels of antioxidant enzymes in a dose-dependent manner. The highest dose of FUPJ (200mg/kg) showed the most significant reduction in the levels of the tested parameters and prevented the gastric mucosal ulceration. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced ulcer and renal dysfunction through its antioxidant and anti-inflammatory properties.