Background: Lipote (Syzygium polycephaloides (C.B. Rob.) Merr.) is an indigenous fruit in the Philippines with potential functions against obesity and non-communicable diseases, but limited literature was available on its safety. Objectives: This study investigated the subacute toxicity effects of freeze-dried fruits of lipote (Syzygium polycephaloides (C.B. Rob.) Merr.) on ICR mice. Materials and Methods: Ten male and ten female 6-week-old ICR mice were divided into two groups: (1) control (vehicle), and (2) lipote group, given with 2000 mg/kg body weight (BW) dose of freeze-dried lipote fruit powder reconstituted in distilled water. Results: After 28 days of oral gavage, the lipote group showed no significant changes on feed and water intake, and hematology and blood chemistry parameters were comparable with those of control group and published normal values. Body weights of all experimental animals also increased significantly (p<0.05), and no mortality, morbidity, or gross and microscopic morphological abnormalities of internal organs were noted. Conclusion: These results showed that 28-day oral consumption of freeze-dried lipote fruits is safe and has LD 50 >2000 mg/kg.