Introduction: Schizophrenia is a psychiatric disease characterized by deficiencies in multiple cognitive domains, such as attention, working memory, long-term memory, and learning, that are stable throughout the patient’s life. Due to mainly focusing on typical symptomatology relief, in many cases, cognitive impairment is overlooked. However, the medication of choice often consists of antipsychotics, their combination being adjusted to the therapeutic response. Yet data regarding the cognitive effects of antipsychotics in schizophrenia is rather scarce and inconsistent. In this context, we aimed to investigate the impact of various combinations of atypical antipsychotics on the cognitive functions of schizophrenia patients. Methods: Thirty participants with schizophrenia were enrolled in the study (18 men and 12 women). The assessment of study participants was conducted by specialized medical personnel, and the application of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) questionnaires aimed to verify cognitive parameters such as spatial–temporal orientation, attention, immediate and short-term memory, the capacity to perform concrete and abstract operations, motor skills, and language. Results: There were differences between the polypharmacy group and the monotherapy group in copying tasks, visuospatial orientation, and attention for both scales involved in this study. Conclusions: Our results suggested that the polytherapeutic approach based on a combination of atypical antipsychotics could lead to the significant improvement of cognitive functions, including spatial and visual orientation, general attention, and verbal memory.