This study evaluated the effects of aqueous homogenates of avocado pear (Persea americana) seeds and fluted pumpkin (Telfairia occidentalis) leaves co-administered with anti-tuberculosis drug on liver enzymes of albino rats. Twenty (20) albino rats were divided into five (5) groups (of four rats each) designated as I, II, III, IV and V (which is the normal control). A dose of 5.14mg/kg body weight of a first line anti-tuberculosis drug (a combination of isoniazid, rifampicin, pyrazinamide and ethambutol) was administered orally to two (2) rats in group I, II, III, and IV for seven (7) days and the remaining two rats in each group for fourteen (14) days. The homogenates of avocado pear seeds (at a dose of 250mg/kg body weight), fluted pumpkin leaves (at a dose of 250mg/kg BW) and a mixture of avocado pear seeds and fluted pumpkin leaves (at a dose of 250mg/kg BW, and 125mg/kg BW respectively) were co-administered with the anti-TB drug to groups II, III and IV respectively. Group I rats served as the positive control (i.e. treated with only 5.14mg/kg BW of anti-TB drug). The results indicated that the activities of serum AST, ALT and ALP were significantly higher (P<0.05) in rats administered with 5.14 mg/kg BW first line anti-TB drugs only when compared with that of the rats co-administered with the same anti-TB drug and 250mg/kg BW plant homogenates (avocado pear seeds, fluted pumpkin leave, and a combination of the two homogenates). The mean serum AST, ALT and ALP activities were found to have decrease (P<0.05) in groups II, III, and IV rats from the beginning to the end of the treatment periods. Similarly, mean serum activities of AST, ALT and ALP in group III rats decreased (P<0.05) significantly when compared with that of group II rats. Moreover, the serum activities of these enzymes were significantly lower (P<0.05) in group V rats compared to that of groups II and III rats. The rise in the mean serum activities of liver enzymes in group I rats when compared to that of group V rats indicated that the anti-TB drug is hepatotoxic. The findings of this research work predicts that the aqueous homogenates of both avocado pear seeds and fluted pumpkin leaves have hepatoprotective abilities but, the combination of these plant parts shows more hepatoprotective function (i. e. exhibits synergy).