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Background: Managing comorbid psychotic disorders and cognitive impairments in community settings is clinically challenging. This study evaluates the real-world impact of Long-Acting Injectable (LAI) antipsychotics on psychiatric hospitalizations, clinical severity, and Quality of Life (QoL) in community-dwelling patients with intellectual or cognitive deficits. Methods: A symmetric, matched-pairs pre-post design was utilized to analyze a targeted cohort of 41 patients from the “DNAng” research project over a six-month observation window. The sample was stratified into two subgroups: a non-hospitalized cohort with primary intellectual disabilities (n = 22) and a previously hospitalized cohort characterized by neuroprogressive cognitive decline and dual diagnoses (n = 19). Main outcomes were tracked using the Clinical Global Impression-Severity (CGI-S) scale and the WHOQOL-BREF Global QoL item. Results: Baseline χ² testing revealed significant sociodemographic and diagnostic differences between the subcohorts (p < 0.05). Following LAI initiation, both groups demonstrated profound, statistically significant clinical improvements. In the non-hospitalized group, CGI-S decreased from 5.77 ± 0.86 to 3.09 ± 0.92 (p < 0.001; δ = 0.97) and QoL rose from 0.59 ± 0.50 to 3.13 ± 0.83 (p < 0.001; δ = -1.00). In the hospitalized group, total admissions plummeted from 2.10 ± 1.28 to 0.05 ± 0.22 (p = 0.0002; δ = 0.98), while involuntary prosecutor-ordered admissions collapsed to near-zero. CGI-S decreased to 3.78 ± 1.08 (p = 0.0003) and QoL reached 3.05 ± 0.84 (p = 0.0001). Conclusions: LAI antipsychotics provide a vital clinical safety net for cognitively vulnerable psychiatric populations, significantly reducing clinical severity, optimizing subjective well-being, and virtually eliminating traumatic and costly involuntary hospitalizations.