Introduction: Numerous physiological and biochemical processes in the human body may produce oxygen-centred free radicals and other reactive oxygen species as by-products. Overproduction of such free radicals can cause oxidative damage to biomolecules, eventually leading to many chronic diseases, such as atherosclerosis, cancer, diabetes, ageing, and other degenerative diseases in humans. A traditional medicine prescription habitually contains various herbs or different parts, and these have a synergistic impact in effecting a cure or reducing toxicity. Aims: The present study was aimed to investigate the effect of a combined extract of Phyllanthus niruri leaves and Sapindus mukorossi fruit on antioxidant activity by in vitro and in vivo methods. Methods: In vitro antioxidant activity was performed by employing 2,2__ampersandsignprime;-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide scavenging, reducing power, hydrogen peroxide scavenging, superoxide anion scavenging and __ampersandsignbeta;- Carotene linoleate assays. In vivo antioxidant estimation has been performed using CCL4 and acetaminophen treated rats. Methanolic extract of Phyllanthus niruri leaves (MEPNL), aqueous extract of Sapindus mukorossi fruit (AESMF) and combined extract (MEPNL+AESMF) responses on antioxidant enzymes (Catalase, SOD and GSH) and lipid peroxidation were evaluated and compared. Results: Combined extract (MEPNL+AESMF) at 400 mg/kg has exhibited significant antioxidant activity in in vitro methods by enhancing the scavenging of DPPH, NO, superoxide anion, increasing the reducing power and inhibition of bleaching of __ampersandsignbeta;-Carotene linoleic acid when compared to individual extracts (MEPNL __ampersandsignamp; AESMF). Lipid peroxidation was significantly decreased with combined extract than individual extracts. Catalase, SOD and Glutathione levels were remarkably elevated with the combination of extracts than individual extracts in CCl4and Paracetamol treated rats. Conclusions: Present study showed that the combined extract of Phyllanthus niruri leaves and Sapindus mukorossi fruit possess significant synergistic antioxidant activity than the individual leaf and fruit extracts demonstrated in vitro and in vivo methods. The synergistic effect of flavonoids, saponins and other antioxidant components in Phyllanthus niruri leaves and Sapindus mukorossi fruits may be responsible for enhanced antioxidant activity.