Hypertension has always posed a severe threat to people’s health. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have the potential to both prevent and treat hypertension. In the current investigation, two ACE-inhibitory peptides (SLPQ and PYVRYL) from goat milk were studied for their endothelial effects using EA.hy926 cells. PYVRYL outperformed SLPQ, yet neither impacted cell survival below 200 μg/mL. Investigation of SLPQ’s impact on EA.hy926 cell expression revealed 114 differentially expressed genes, with 65 downregulated and 49 upregulated. The genes were enriched in cytokine interactions, coagulation cascades, Hippo signaling, and ECM–receptor interaction. Decreased c-x-c motif chemokine ligand 2 (CXCL2), integrin subunit beta 2 (ITGB2), and fbj murine osteosarcoma viral oncogene homologue (FOS) expression and increased secreted phosphoprotein 1 (SPP1) expression may protect endothelial cells from inflammation. Our findings suggest that beyond ACE inhibition, SLPQ aids blood pressure control by influencing endothelial function, paving the way for its use as an antihypertensive food ingredient.