Objectives. Antimicrobial activity of extract of prickly pear (Opuntia ficus-indica var. saboten Makino; OFI) has been reported. This study examined effects of OFI extract on the growth of Streptococcus mutans. Methods. OFI was extracted by 85% methanol using an ultrasonic extraction method. The agar plate dilution method was used to count the CFU of viability of S. mutans KCTC 3065 that was determined by enumeration (colony forming units) in an agar dilution assay using no OFI (control), or 5, 20, and 50 mg/mL OFI following incubation for 0, 6, 12, and 24 h. The cytotoxicity of OFI extract (0, 5, 10, 20, 40, 50 mg/mL) was evaluated for human gingival fibroblasts by a formazan-based viability. Results. S. mutans growth was reduced by the OFI extract. The number of viable S. mutans was reduced significantly with increasing OFI concentration and incubation time (both p＜0.001). The viable counts of S. mutans cultured with 20 and 50 mg/mL OFI decreased gradually but appreciably (＞88.7%) by 6 h and no S. mutans remained when cultured with 50 mg/mL at 24 h. OFI concentrations of 40 and 50 mg/mL were cytotoxic to fibroblasts. Conclusions. OFI displays S. mutans inhibitory activity, and may be potential exploited as an oral hygiene agent for the prevention of dental caries.