The present study aims to emphasize the enhanced efficacy of long acting in-situ gel forming implants (ISGFI) based on poly (lactic-co-glycolic acid) (PLGA) matrix to deliver anti-psychotic risperidone over extended time periods with reduced administration frequency. Schizophrenic patients show considerable difficulties in adherence and compliance to oral medications associated with negative outcomes including symptoms exacerbation and psychotic relapse. The studied optimized ISGFI formulation, comprised of 2.85:1 ratio of DMSO solvent:PLGA (type 75:25), was subjected to various characterization studies including morphological real-time changes, scanning electron microscopy and in-vitro drug release study. Pharmacokinetics and behavioral evaluations of anti-psychotic action of ISGFI systems were pursued on healthy and schizophrenia-induced rats respectively then compared to results of marketed microspheres. Morphological observations showed the immediate formation of whitish smooth ISGFI system owing to the rapid PLGA solidification after rapid DMSO dissipation into the external medium. Scanning electron microscopy confirmed the slow gradual biodegradation of the formed ISGFI. The optimized formulation assured its effectiveness to produce satisfactory initial burst and cumulative risperidone release and obviate costs of additional tablets needed during the commercial product use. Pharmacokinetic study manifested the effective performance of ISGFI to extend risperidone release for longer period (72 days) in comparison to the marketed formulations (48 days). Besides, optimized ISGFI were more effective in improving ketamine-induced schizophrenia-like symptoms in experimental rats, particularly in the first week of study period. Meanwhile, in-vitro, pharmacokinetic and pharmacodynamic evaluations had advocated the potential advantages of ISGFI systems for treating schizophrenia with improved adherence and compliance of patients.