Elevated cholesterol levels can lead to various diseases and reduce quality of life, including non-alcoholic fatty liver disease (NAFLD), which poses a growing global health concern. Andrographis paniculata (sambiloto) contains andrographolide, a bioactive compound known to inhibit cholesterol synthesis, suggesting its potential as a herbal alternative to manage hypercholesterolemia. This study aimed to evaluate the effect of sambiloto leaf extract (Andrographis paniculata Nees) on the liver histopathology of male Wistar rats (Rattus norvegicus) fed a high-cholesterol diet. This true experimental laboratory study used a post-test control group design with randomized probability sampling. Rats were divided into six groups: normal control, negative control, positive control (atorvastatin), and three treatment groups receiving sambiloto extract at doses of 200, 400, and 800 mg/kgBW. Liver histopathology was assessed using the NAFLD Activity Score (NAS), and data were analyzed using the Kruskal–Wallis test followed by post hoc LSD analysis. The results showed a significant effect of sambiloto extract on liver histopathological changes (p = 0.028, p < 0.05), although no significant differences were observed among the different dosage groups. In conclusion, sambiloto leaf extract has a significant influence on improving liver histopathological profiles in male Wistar rats fed a high-cholesterol diet.