Hemp seed milk is an emerging plant-based dairy alternative with high nutritional value; however, its digestibility and nutrient bioaccessibility remain underexplored, particularly in relation to compositional factors such as fat content. This study provides a novel comparative analysis of the in vitro digestion behavior of dehulled full-fat and fat-reduced hemp seed milks, marking one of the first investigations to link fat reduction with protein digestibility, coagulation dynamics, and nutrient bioaccessibility. Milk samples were developed using optimized processing parameters: a 5.23% seed-to-water ratio at pH 8.26 for full-fat and 11.1% at pH 8.5 for fat-reduced variants combined with ultrasound homogenization and thermal pasteurization. Simulated oral, gastric, and intestinal digestion phases were performed using a modified static in vitro protocol. Analytical parameters included gastric pH trends, coagulation behavior, SDS-PAGE protein profiling, and the protein bioaccessibility index (BI). The fat-reduced formulation showed superior protein bioaccessibility (72.76%) compared to the full-fat formulation (66.41%), likely due to reduced lipid interference and improved intestinal diffusivity. Notably, it exhibited delayed but firmer coagulation and a slower gastric pH decline, indicating better physical and buffering stability—a desirable trait in functional beverage design. In contrast, full-fat milk showed rapid curd formation and earlier phase separation. While protein digestibility increased with time in both samples, the full-fat milk reached higher final digestibility (84%) due to faster enzymatic hydrolysis, whereas the fat-reduced milk demonstrated slower but more sustained degradation, consistent with its higher protein content. This work aligns with the "Food Technology and Engineering" theme by integrating formulation optimization, process engineering (ultrasound and pasteurization), and in vitro digestion modeling to evaluate the structural and functional performance of novel plant-based milks. The findings offer technological insights into tailoring fat content to enhance bioaccessibility and stability, supporting the development of clean-label, nutritionally functional beverages.