Aim: The aim of this work was to develop extended-release risperidone nanoparticles for parenteral delivery (intravenous) and to reduce the dose-dependent extrapyramidal side effects of risperidone. Methods: Polymeric nanoparticles containing risperidone made of poly (ε-caprolactone) were designed by the nanoprecipitation method using polymeric stabilizers (poloxamers). The in vivo efficacy of prepared formulations and the risperidone solution was studied by administering them intravenously to apomorphine-treated mice. Extrapyramidal side effects of the risperidone and its formulations were also studied. Results: The particle size of the prepared nanoparticles ranged between 99 and 304 nm. Approximately 78–85% drug-encapsulation efficiency was achieved when risperidone was loaded at 1.7–4.1% by weight of the polymer. During in vivo studies, prepared risperidone-containing formulations showed a significant prolonged antipsychotic effect than that of risperidone solution, also having less extrapyramidal side effects. Conclusion: The prolonged effect of risperidone was obtained from the nanoparticles of risperidone administered by the intravenous route and this may improve the treatment of psychotic disorders by dose reduction.