A fermentation process-derived mogroside mixture (≥91.9% total mogrosides) containing high levels of siamenoside I (≥73%) was assessed in a bacterial reverse mutation assay, in vitro micronucleus assay, 28-day repeat-dose dose range-finding study, and 90-day repeat-dose oral toxicity study. Mogrosides, including siamenoside I, are cucurbitane glycoside derivatives of monk fruit (Siraitia grosvenorii) recognized as natural sweeteners. While monk fruit extracts containing concentrated levels of mogrosides (primarily mogroside V) have been marketed in the United States and evaluated by the European Food Safety Authority (EFSA), a safety assessment of fermentation process-derived mogrosides has not been previously conducted. No biologically-relevant mutagenic or genotoxic effects were reported in a bacterial reverse mutation or in vitro micronucleus assay conducted per Good Laboratory Practices (GLP) and relevant OECD test guidelines (OECD TG 471; OECD TG 487) at concentrations up to 5000 µg/mL in each study. A no-observed-adverse-effect level (NOAEL) of 50,000 ppm (calculated time-weighted average [TWA] equivalent to 4410 mg/kg-bw/day in males and 4112 mg/kg-bw/day in females) was reported in a non-GLP-compliant 28-day dose-range finding study. Similarly, in the 90-day study conducted per GLP in accordance with OECD TG 408 at concentrations of 0, 12,500, 25,000, or 50,000 ppm in the diet, the NOAEL was 50,000 ppm in male (calculated TWA equivalent to 3309 mg/kg-bw/day) and female rats (calculated TWA 3362 mg/kg-bw/day). In the context of low anticipated consumer exposure in adults and children, these results support the safety of this mogroside mixture in foods.