Objective This study investigated the therapeutic efficacy of Rhizoma Alisma in isoproterenol(ISO)-induced myocardial fibrosis(MF) in SD rats, with a mechanistic focus on modulation of the pyroptotic pathway. Methods Rats were randomly allocated into five groups (n=8 per group): control(NC) group, MF group, Captopril(CAP) group, low-dose Rhizoma Alisma(RAL) group, and high-dose Rhizoma Alisma(RAH) group. MF was induced via ISO administration. Serum levels of CK-MB, α-HBDH, and LDH were quantified. Cardiac tissue morphology was assessed using HE and Masson staining. Western blot analysis determined the expression levels of α-SMA, NLRP3, Caspase-1, and GSDMD proteins, while laser confocal microscopy visualized Collagen I deposition in myocardial tissue. Results ISO induction triggered severe MF in rats, evidenced by histopathological collagen deposition and elevated NLRP3, Caspase-1, and GSDMD expression. Rhizoma Alisma treatment reduced serum levels of CK-MB, α-HBDH, and LDH, ameliorated tissue damage, downregulated collagen deposition, and significantly suppressed the expression of NLRP3, Caspase-1, and GSDMD. Conclusion Rhizoma Alisma demonstrates significant efficacy in attenuating ISO-induced MF, potentially through modulation of cell pyroptosis.