Background and Objective: Paullinia pinnata is an African woody vine whose leaf decoction has been used in Cameroon for the treatment of bacterial infections like typhoid fever, syphilis, gonorrhea, diarrhoea and symptoms such as stomach-ache and waist pain. The present study was designed to evaluate the adverse side effects resulting from the use of P. pinnata methanol leaf extract in the treatment of Salmonella typhimurium-induced typhoid in Wistar rats. Methodology: After the establishment of infection by oral administration of a S. typhimurium suspension, animals were treated by the daily administration of P. pinnata methanol leaf extract at various doses (55.75, 111.50, 223 and 446 mg kgG 1 b.wt.). The effect of the extract on body weight evolution was monitored daily. Results: Also, the effect of the extract on relative organ weight, biochemical parameters as well as liver histology was assessed. Irrespective of sex, typhoid fever induced an abnormal increase in the relative weight of most vital organs of toxicological importance. However, extract treatment normalized the excessive increase in relative organ weights; while inducing a significant (p<0.05) body weight gain in a dose-dependent manner. The level of liver enzymes (ALT and AST) were significantly (p<0.05) reduced after the treatment of the animals with P. pinnata leaf extract. The histopathological analysis of the liver revealed that extract treatment greatly reduced the degree of liver affections in a dose-dependent manner. However, at high doses (dose $223 mg kgG 1 b.wt.) the extract was capable of stimulating hepatic necrosis. Conclusion: The overall results of this study indicate that the methanolic extract of P. pinnata leaves has hepatoprotective effects especially in males. It has adverse side effects at high doses and even at low doses in female rats and thus, should be used with caution in male and should probably be eliminated from the treatment of female subjects.