Like orthodox drugs, plant-based medicines have been known to interact with and affect bioactive molecules and functions. Our earlier study using HPLC in quantification of bioactive compounds revealed high levels of quercetin, gallic acid, and rutin in Psychotria vogeliana leaf. In this study, the effects of Psychotria vogeliana leaf ethylacetate fractions on the liver, kidney, and cytokine levels in albino rats with rheumatoid arthritis were investigated. Out of the 48 total, six groups of 8 female rats each were constituted. Rats in Group A were used as the standard control group, and they were given simply normal saline. With 0.1 ml of complete Freund's adjuvant (CFA), rheumatoid arthritis was induced in Group B (toxic control). Rats in group C were given standard drug (methotrexate) after being infected with rheumatoid arthritis. Rats in groups D, E, and F were given ethyl acetate extract fraction of Psychotria vogeliana leaf at 200 mg/kg, 400 mg/kg, and 600 mg/kg body weight, respectively, for 28 days after being provoked with rheumatoid arthritis using CFA. Oral intubation was used to provide the dosages to the animals, and a heart puncture was used to obtain blood samples for biochemical examinationS. Using standard techniques, the following biochemical indices were measured: interleukin-6 (IL-6), interleukin-1 β (IL-1β), albumin, total bilirubin, alkaline phosphatase, creatinine, blood urea nitrogen (BUN), urea levels, and Tumour Necrosis Factor-alpha (TNF-α). The levels of IL-6, IL-1β, TNF-α, urea, creatinine, BUN, AST, ALT, and ALT were found to be notably (P<0.05) increased in the rheumatoid arthritis rats than in the control group. In contrast, levels of albumin and total bilirubin were drastically (p<0.05) decreased. The effects of CFA in rats with rheumatoid arthritis were significantly reversed (P<0.05) when the extracts were administered at the prescribed dosages. The extracts showed both time and dose-dependent ameliorative effects on arthritic rats, with their anti-arthritic potentials comparable to that of the standard drug. The extract effectively treated arthritis by restoring liver, kidney, and cytokine levels against the toxic group.