Background: Mitragyna speciosa Korth possesses a wide range of therapeutic benefits, despite having abuse liability. Objectives: The purpose of this research was to investigate the reinforcing properties of M. speciosa Korth leaf extract obtained via methanol extraction using mouse conditioned place preference (CPP) test. Materials and Methods: In CPP study, following baseline preference test (preconditioning score), the mice were subjected to conditioning trials at varying doses of methanolic extract of M. speciosa (MMS, 50, 75, 100, 250, 500, and 1000 mg/kg, p.o.) or reference drugs methamphetamine (0.5 mg/kg, intraperitoneally [i.p.]) and clozapine (1 mg/kg, p.o.) or vehicle controls (1% w/v sodium carboxy methyl cellulose [10 mL/kg, p.o.] and saline [10 mL/kg, i.p.]) followed by a preference test performed under drug-free state (postconditioning score). In addition, the effect of all tested drugs on the spontaneous locomotor activity was assessed. Results: The CPP study results revealed that MMS per se produced a significant place preference only at higher doses (>500 mg/kg, p.o.). Nevertheless, MMS at lower doses (50–250 mg/kg, p.o.) did not induce CPP in mice. In addition, MMS at all tested doses (50–1000 mg/kg, p.o.) did not affect the spontaneous locomotor activity in mice. Conclusion: MMS per se exhibits reinforcing properties at only an increased dose of >500 mg/kg, and therefore, it is best to administer at lower doses (<250 mg/kg) for the potential therapeutic benefits in preclinical studies.