Cardiovascular disease (CVD) remains a major global health issue, closely associated with the excessive intake of saturated fatty acids (SFAs). High SFA consumption contributes to elevated cholesterol levels and vascular obstruction, emphasizing the need for healthier alternatives in food products. One promising strategy is the development of functional shortening with reduced SFA content. This study aimed to optimize the ratio of Glycerol Monostearate (GMS) and Sorbitan Monostearate (SMS) to improve the lipid profile of low-saturated fat shortening using integrated lipidomic and chemometric approaches. The experiment involved two concentrations of GMS:SMS (5% and 10%) with six formulations each: 100:0, 80:20, 60:40, 40:60, 20:80, and 0:100, prepared in triplicate. Lipid profiling was conducted using lipidomic analysis, along with standard assessments such as free fatty acid (FFA) content, peroxide value (PV), and fatty acid composition via Gas Chromatography–Mass Spectrometry (GC-MS). Multivariate analyses, including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), were employed to interpret the complex dataset. Among the formulations, three under the 5% GMS:SMS group (100:0, 80:20, and 60:40) showed the best oxidative stability based on FFA and PV. Notably, the 5% GMS:SMS (80:20) formulation demonstrated the most favorable lipidomic profile, marked by a higher number of unsaturated lipid species (39 in ESI+) and reduced SFA content (12 in ESI+). These findings highlight the potential of GMS and SMS as structuring agents in designing low-saturated shortening products with improved lipid profiles, offering a viable strategy for the development of heart-healthier fat-based food products.