This study aimed to evaluate the potential preventative effects of Andrographis paniculata on cardiac damage produced by diclofenac in Wistar albino rats. The rats were randomly assigned to five groups: Group 1, which served as the normal control and was given only feed; Group 2, which served as the positive control and was given feed along with 100 mg/kg body weight diclofenac; Group 3, which received feed along with 100 mg/kg body weight diclofenac and 200 mg/kg extract; Group 4, which received feed along with 100 mg/kg body weight diclofenac and 400 mg/kg extract; and Group 5, which received feed along with 100 mg/kg body weight diclofenac and 200 mg/kg vitamin E. The oral administration of the extract was conducted over a period of 14 days, following which the animals were slaughtered on the 15th day in order to facilitate subsequent analysis. The findings indicated that administering Andrographis paniculata extract to the experimental groups led to a statistically significant increase in bodyweight for group 3 (167.33 ± 21.33) and group 4 (173.33 ± 17.63), as compared to the normal and positive control groups (p<0.05). The research findings demonstrated a clear association between diclofenac administration and cardiac damage, with a statistically significant elevation in blood concentrations of total cholesterol, triglycerides, low-density lipoprotein, and malondialdehyde. Pretreatment with Andrographis paniculata resulted in a modulation of the decrease in levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) in group 2 compared to group 1. However, the administration of Vitamin E led to a significant decrease in serum total cholesterol (TC) level, triglyceride (TG), low-density lipoprotein (LDL) level, and malondialdehyde (MDA) levels, as well as an increase in serum high-density lipoprotein (HDL) level, superoxide dismutase (SOD), and catalase (CAT) activity compared to the positive control. ....