This study presents a comprehensive methodology for the synthesis, characterization, and evaluation of selenium nanoparticles (SeNPs) for their anthelmintic properties against Trichinella spiralis. SeNPs were synthesized via a chemical reduction method, with a color change from clear white to brownish-red indicating nanoparticle formation. X-ray diffraction (XRD) analysis revealed broad peaks at 2θ ranges of 20-33° and 48-58°, confirming the semi-crystalline nature of the nanoparticles. UV-Vis absorption spectroscopy identified a characteristic peak at around 295 nm. High-resolution transmission electron microscopy (HRTEM) showed spherical, monodispersed SeNPs with smooth surfaces, ranging from 30 to 106 nm in size, with an average diameter of 69 nm. Forty-two male rats were divided into six groups, including healthy controls and T. spiralis-infected rats treated with varying doses of SeNPs. Body and organ weight indexes were assessed at the start, during the intestinal and muscular phases. Significant body weight increases were observed during the intestinal phase, particularly in the positive control group. Organ weight analysis showed a significant decrease in liver weight in the high-dose SeNP group compared to controls. SeNP treatment significantly reduced the number of adult worms in the intestines and encysted larvae in muscles. The high-dose group reduced adult worms and encysted larvae more than the low-dose group. Scanning electron microscopy (SEM) revealed morphological alterations in adult T. spiralis worms, including wrinkled architecture, torn cuticles, and severe sloughing in high-dose treated worms. During the muscular phase, significant decreases in hemoglobin and red blood cell count were observed in the positive control group, while SeNP treatment restored these levels. Liver enzyme activities (AST, ALT, and ALP) were elevated in infected untreated groups but were enhanced with SeNP treatment. Antioxidant enzyme activities (CAT, and SOD) increased in SeNP-treated groups, with higher doses showing greater efficacy in reducing oxidative stress markers (MDA) and inflammatory markers (TNF-α, and IL-6). Histological analysis showed significant restoration of normal intestinal architecture in high-dose SeNP-treated infected rats, including the reduction of villus atrophy and leukocyte infiltration. In diaphragm muscles, high-dose SeNP treatment minimized encysted larval deposition and restored normal muscle architecture. We can conclude that the study demonstrates the potential of SeNPs as an effective anthelmintic agent against T. spiralis, highlighting their synthesis, characterization, and therapeutic efficacy.