Introduction Although spironolactone and telmisartan are reported to reduce the risk of morbidity and death, direct studies on their effects on isoproterenol-induced cardiac hypertrophy are scanty. Hence the present investigation was carried out to study the effect of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy. Methods Isoproterenol was administered intra-peritoneally in a dose of 5 mg/kg once daily for 10 days to Wistar rats. Spironolactone (20 mg/kg/day) (SL), telmisartan (5 mg/kg/day) (TM) or their combination (SLTM) was administered for 10 days after which various biochemical and cardiac parameters were measured. Results Isoproterenol produced dyslipidaemia, hypertension, elevated cardiac enzyme and C-reactive protein levels (CRP), worsened haemodynamic parameters and produced cardiac hypertrophy, left ventricular (LV) hypertrophy and oxidative stress. Chronic treatment with SL, TM or SLIM significantly controlled dyslipidaemia and produced a significant reduction in the elevated creatine-kinase (CK) and CRP levels. TM or SLIM produced a decrease in elevated lactate de-hydrogenase levels; however, SL failed to produce this effect. Hypotension, tachycardia, and decreased rate of pressure development and decay were prevented by SL, TM and SLIM treatment. Chronic treatment with SL,TM or SLTM also produced significant reduction in LV collagen levels, cardiac and LV hypertrophy index and prevented oxidative stress. Conclusions Our data suggests that SL, TM and SLIM produced a beneficial effect on cardiac hypertrophy.