Modulating the brain renin-angiotensin system presents an innovative pathway for exploring newer treatment approaches in epilepsy. The current study aimed to evaluate the influence of losartan (LOS) and enalapril (ENP), which are angiotensin receptor blocker and angiotensin-converting enzyme inhibitor, respectively, on the incidence, initiation, and duration of status epilepticus (SE), spontaneous convulsive seizures (SCS), survival, and cardiac alterations in rats subjected to lithium-pilocarpine (LiP)-induced SE. Lithium (127 mg/kg, i.p.) pretreated male Wistar rats were administered pilocarpine (30 mg/kg, i.p.) after 24 h to induce SE, which was terminated after 90 min of onset. Daily 10-h video monitoring was carried out for examining onset, frequency, duration of SCS, and mortality till 18 days. The administration of LOS (10 mg/kg, i.p.), ENP (20 mg/kg, i.p.) and atenolol (AT; 50 mg/kg, p.o.) was started before lithium in pre-SE protocol and for post-SE protocol these drugs were administered 1 h after terminating SE and continued for 7 days’ post-SE. Cardiac pathology, echocardiography, heart weight/body weight ratio, and histopathology were evaluated. None of the drugs used (LOS/ENP/AT) offered protection against SE. Administration before SE decreased and post-SE administration increased the latency of SCS, and the overall duration of seizures remained short in both cases as compared to untreated rats. The heart weight/body weight ratio decreased in rats that did not survive. No echocardiographic changes were observed in any of the groups. Untreated SE rats showed myocyte ischemic changes, which were not present in any treated rats. In conclusion, LOS may reduce cardiac complications in SE rats. Hence, further evaluation of LOS as an add-on in epilepsy treatment should be performed.