Sweet potato (Ipomoea batatas (L.) Lam) is an important food and energy crop. Soil salinization is a major abiotic stress that limits agricultural productivity and severely reduces yield of crops. Protein hydrolysates, as a class of natural biostimulants, have gained increasing attention for their potential to improve crop yield, quality and stress tolerance. This study investigated the effects of peptides from swine blood (PSB) on high salinity stress tolerance in sweet potato. Application of PSB promoted the growth of both aerial and underground parts of sweet potato under normal and high-salinity conditions. Further analysis revealed that, under high salinity stress, exogenous PSB up-regulated the expression of genes associated with stress responses, increased the accumulation of organic osmotic adjustment compounds such as free amino acids, promoted K⁺ uptake to elevate the K⁺/Na⁺ ratio, and enhanced the activity of key antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) involved in the reactive oxygen species-scavenging system. These biochemical responses contributed to maintaining cellular osmotic balance and redox homeostasis, protecting the cell membrane from damage while preserving its structural integrity and normal physiological functions, and improving photosynthetic efficiency, thereby enhancing high salinity stress tolerance in sweet potato. Thus, PSB holds significant potential as an effective natural biostimulant for sweet potato cultivation in saline soils.