Background & Aim: Diclofenac sodium (DFS) is a drug used for treatment of pain in humans and animals. Plant extracts have been used by the herbalists for treatment of hepatorenal disorders in humans for many years without scientific evidence. The present study evaluated the effects of Byrsocarpus coccineus, Dialium guineense, and Newbouldia laevis extracts (BCE, DGE and NLE respectively) on DFS-induced hepatorenal damage in rats and compared their efficacies. Experimental: Rats were divided into 5 groups with 5 rats per group. The rats in group 1 were injected with normal saline while those in group 2 were injected with11 mg/kg DFS intramuscularly for 5 days. The rats in groups 3, 4 and 5 were injected with DFS like group 2 rats but treated with 342 mg/kg BCE, DGE and NLE respectively for 6 days. About 24 hours after treatment, blood was collected from a rat, serum was separated, and used for the estimation of biochemical parameters. The rats’ liver and kidneys were removed and histological examinations were performed on the tissues of animals. Results: There were significant (P<0.05) alterations in the levels of biomarkers of hepatorenal injuries in rats treated with DFS when compared with the control. The treatment of DFS-exposed rats with BCE, DGE and NLE significantly (P<0.05) reversed the altered markers of hepatorenal injuries when compared with the DFS group. The photomicrographs of hepatorenal tissues showed microstructural features which corroborated our biochemical findings. Recommended applications/industries: These findings suggest that the three plant extracts have ameliorative effects on DFS-induced hepatorenal injuries in rats but DGE has the greatest efficacy. Therefore, they may be processed and utilized for the treatment of hepatorenal injuries in animals. Manuscript profile