In a trial lasted for 90 days to assess the impacts of ration supplementation with saponin containing plant extract (defaunator) (SCPE) without or with fresh baker's yeast culture Saccharomyces cerevisiae (Probiotic) (FSCYC) as feed additives to enhance rumen fermentation in lactating buffalo cow. Twenty lactating buffalo cows of an average weight of 591 Kg were allotted to four groups of five animals each according to age and assigned at random to receive one of four dietary treatments. The treatments were: T1, (Control) received the Basal ration BR that consists of concentrate feed mixture: Egyptian berseem: rice straw (50:25:25 %, on dry matter basis), T2, received the BR plus 800 mg. saponin from the SCPE, T3, received the BR plus 800 mg  saponin plus 10 gm's  FSCYC,  and T4 received the BR plus 800 mg saponin plus 20 gm's of FSCYC respectively. Results of ration supplementation of saponin without or with 10 or 20 gm's FSCYC treatments T2, T3, and T4 increased (P<0.05) nutrients digestibility, milk yield, milk protein, fat, lactose, total solids and solids not fat contents. Additives supplementation also increased blood serum total proteins, albumin (A) and globulin (G); however it decreased (P<0.05) A/G ratio, cholesterol and GPT.  Treatment  (T4) exhibited the highest (P<0.05) nutrients digestibility coefficients, milk yield, milk constituents, protein and fat, and blood serum proteins, albumin and globulin, but the lowest (P<0.01) blood serum urea, cholesterol, GOT and GPT wre obtained the treatment T4. It could be concluded that ration supplementation with SCPE plus 10 or 20 gm's of FSCYC for lactating buffalo cows (especially T4) had beneficial effects on their productive performance with normal physiologic responses of the cows. Key words: fresh baker's saccharomyces cerevicia yeast, natural saponin plant extract, lactating buffaloes, nutrients digestibility, milk yield, constituents, blood serum.