Exertional rhabdomyolysis (ER) is a condition where muscle breakdown occurs after intense and unaccustomed exercise in healthy individuals. It is characterized by muscle pain, weakness, and myoglobinuria, potentially leading to acute kidney injury and worsening the patients’ prognosis. Ultra-trail races (UT) necessitate high energy and extreme muscular exertion, which can result in significant muscle breakdown, leading to ER and elevated biomarkers such as creatine kinase (CK) and lactate dehydrogenase (LDH). These races involve longer durations and both uphill and downhill elevations, with the latter causing more muscle damage. This systematic review aims to analyse the effect of downhill elevation (at least 1000 m) in UT on muscle and liver damage biomarkers. We conducted a systematic review of four electronic databases (Pubmed, Web of Science, Scopus, and Sportdiscus) based on PRISMA guidelines for systematic reviews. We included a total of 15 articles out of 6670 published between January 2005 and March 2024. The total population sample included 348 subjects, comprising 294 men (84.48%) and 54 women (15.52%) with a mean age of 39.82 ± 6.89 years. Only one subject (0.28%) was diagnosed with ER. The median increase in CK post vs. pre was 5370.63 ± 7289.71%, LDH post vs. pre was 311.20 ± 164.4%, and liver damage biomarkers aspartate transaminase (AST) and alanine aminotransferase (ALT) obtained mean increases of 1009.94 ± 743.97% and 207.02 ± 92.84%, respectively. No liver injury cases were reported. These findings suggest that ER is often misdiagnosed in UT and may result in acute kidney injury under certain circumstances. Therefore, it is crucial to define and prepare the characteristics required for ultra runners to safely participate in these extreme races.