Statin therapy, particularly atorvastatin, is widely used for lowering LDL-C and reducing cardiovascular risk. However, statin intolerance due to muscle-related symptoms and hepatotoxicity affects long-term adherence, necessitating the exploration of alternative lipid-lowering agents. Guggul (Commiphora mukul), a natural remedy used in Ayurvedic medicine, has been suggested as a safer alternative due to its cholesterol-modulating effects and favorable safety profile. This study aimed to compare the safety and tolerability of atorvastatin and Guggul in hyperlipidemic patients by evaluating adverse event incidence, liver enzyme elevations, and muscle toxicity markers. A 12-week randomized controlled trial (RCT) was conducted with 150 hyperlipidemic patients receiving either atorvastatin (10 mg/day) or Guggul (2000 mg/day). Muscle pain was significantly higher in atorvastatin users (24%) compared to Guggul users (10.6%, p < 0.01). Liver enzyme elevations were observed in 6.7% of atorvastatin users but not in the Guggul group (p < 0.01). Severe CK elevations (>5× ULN) occurred in 8% of atorvastatin users, with no cases reported in Guggul users. While mild gastrointestinal discomfort (13.3%) and skin rash (5.3%) were observed in Guggul users, no severe adverse events were reported. These findings suggest that Guggul may offer a safer alternative for patients experiencing statin intolerance, though further long-term studies are required to confirm its cardiovascular safety.