Background: This study investigates the possible synergistic influence of probiotics, specifically Lactobacillus acidophilus (LA) and Bacillus coagulans (BC), in conjunction with Simvastatin (SMV) for treating Rhabdomyolysis in hypercholesteremic rats. Aim: The study aims to evaluate the combined effects of SMV with LA or BC on various health parameters in hypercholesteremic rats induced with rhabdomyolysis. Methods: Hypercholesteremic rats with rhabdomyolysis were treated with SMV, LA, BC, and combinations of SMV with LA or BC. The study measured body weight, lipid profiles, renal function, skeletal muscle, and inflammation markers. Results: The combination treatments showed promise in reducing body weight gain. Regarding lipid profiles, SMV in tandem with LA demonstrated slightly enhanced efficacy in lipid regulation compared to other combinations. Both probiotic strains exhibited substantial potential in preserving nephron function alongside SMV. Probiotic combinations with SMV helped mitigate skeletal muscle dysfunction. Regarding inflammation, both combinations alleviated inflammation symptomatic of rhabdomyolysis. Notably, BC, combined with SMV, excelled in dampening inflammatory cytokines like TNF-α and IL-6, surpassing LA. Conclusion: The combined administration of SMV with LA or BC effectively mitigates rhabdomyolysis-induced issues, with varying impacts on diverse outcomes. Future investigations are imperative to comprehensively ascertain the optimal probiotic regimen for managing rhabdomyolysis. These positive outcomes underscore the multifaceted roles of probiotics in addressing rhabdomyolysis-related complications, emphasizing the necessity for further exploration into their mechanisms and clinical implications.