The purpose of this study was to assess the cardioprotective potential of Phyllanthus maderaspatensis L. Quantitative phytochemical analysis and gas chromatography-mass spectrometry (GC-MS) of solvent extracts were performed. Standard antioxidant assays were used to determine the free-radical scavenging activity of the leaf extract. An in vivo experiment using isoproterenol (ISO)-treated rats was conducted to assess the effect of the plant extract on cardioprotective biomarkers. A significant dose-dependent increase in total antioxidant activity of the extract was observed. At 50 µg, 19–24 % scavenging activity was recorded, whereas at 400 µg, 79–84 % scavenging activity was observed. Rats receiving the extract showed a reduction in heart weight and an increase in body weight. The mean serum concentration of cardiac troponin (cTn) T/I in rats treated with the standard drug was effectively reduced (1.13 ± 0.07/0.64 ± 0.05 ng mL-1), whereas it was comparably reduced by the extract (1.25 ± 0.19/0.72 ± 0.08 ng mL-1). Creatine kinase MB (CK-MB) of the standard was significant at 78.33 ± 6.26 IU and the extract was 83.35 ± 7.51 IU. The data showed increased values among the standard and extract compared to the control group but were found to be significantly (p <0.001) decreased among the treated groups. Compared to negative control animals (healthy rats), ISO-treated rats exhibited significantly increased levels of aspartate myocardial cell damage. After 5 weeks of treatment, in comparison to those in the positive control (PC), extract-treated rats had significantly (p <0.05) elevated levels of serum AST, alanine transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Recovery from ISO-induced electrophysiological abnormalities was confirmed by decreased serum cardioprotective markers, mainly troponin and CK-MB. Histopathological damage to cardiac tissues was significantly reduced, with values approaching those of the control and standard drug-treated groups, particularly at a dose of 200 mg kg-1 body weight (bwt). The findings confirm that the cardioprotective effects are primarily attributable to the presence of antioxidant constituents present in the extract of P. maderaspatensis.