Psidium guajava leaf is reported to contain many bioactive polyphenols which play an important role in the prevention and treatment of various diseases. Our investigation aimed to study the effect of Psidium guajava leaf powder supplementation on obesity and liver status by using experimental rats. To study the effects of guava leaf supplementation in high fat diet induced obesity, rats were randomly divided into four experimental groups (n=7), control (group I), control + guava leaf (group II), HCHF (group III), and HCHF + guava leaf (group IV). At the end of the experimental period (56 days), glucose intolerance, liver enzymes activities, antioxidant enzymes activities, and lipid and cholesterol profiles were evaluated. Our results revealed that guava leaf powder supplementation showed a significant reduction in fat deposition in obese rats. Moreover, liver enzyme functions were increased in high fat diet fed rats compared to the control rats significantly which were further ameliorated by guava leaf powder supplementation in high fat diet fed rats. High fat diet feeding also decreased the antioxidant enzyme functions and increased the lipid peroxidation products compared to the control rats. Guava leaf powder supplementation in high fat diet fed rats reduced the oxidative stress markers and reestablished antioxidant enzyme system in experimental animals. Guava leaf powder supplementation in high fat diet fed rats also showed a relative decrease in inflammatory cells infiltration and collagen deposition in the liver compared to the high fat diet fed rats. The present study suggests that the supplementation of guava leaf powder prevents obesity, improves glucose intolerance, and decreases inflammation and oxidative stress in liver of high carbohydrate high fat diet fed rats.