The current study aimed to investigate the molecular toxic effects of zinc sulfide (ZnS) and zinc sulfide nanoparticles (ZnS-NPs) on rat skeletal muscle tissue. It also explored the forensic implications of ZnS toxicity on postmortem carrion infestation, particularly its potential impact on postmortem interval (PMI) estimation. ZnS nanoparticles were synthesized and characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Thirty Wistar rats were divided into three groups: control, ZnS-treated, and ZnS-NP-treated (both administered at the LD50 dose of 2000 mg/kg). Muscle tissues were harvested for histopathological, ultrastructural, and acridine orange staining analysis. Arthropods were collected and identified across five decomposition stages to assess changes in carrion infestation patterns. Histopathological and ultrastructural analysis showed marked deformation, necrosis, and degeneration of muscle fibers, more severe in the ZnS-NP group. Collagen deposition significantly decreased in both treatment groups. Electron microscopy revealed dissociation and degradation of myofibrils with increased interfibrillar spacing. Arthropod analysis indicated altered colonization patterns, with decreased adult abundance and disrupted succession stages, especially during the active decay phase. ZnS and ZnS-NPs induce significant skeletal muscle toxicity that may mimic postmortem autolysis and lead to PMI misinterpretation. ZnS-NPs exert more severe effects than bulk ZnS. The observed entomological disruption highlights the forensic relevance of ZnS exposure and underscores the need for integrated toxicological and entomological analyses in PMI estimation.