This study aimed to screen for functional lactic acid bacteria (LAB) with the potential to prevent hyperglycemia, hyperlipidemia, and hypertension (collectively termed the “three highs”). Totally 20 strains with high acid and bile salt tolerance were selected from 76 LAB isolates. These strains were then evaluated for their inhibitory activities against α-glucosidase, α-amylase, pancreatic lipase, and angiotensin-converting enzyme (ACE), as well as their antioxidant capacity. Principal component analysis (PCA) and entropy-weighted TOPSIS were used to identify the two most promising strains against the “three high”: Lactiplantibacillus plantarum L.P 06 and Lacticaseibacillus paracasei L.Pc 02. Among the 20 strains, L.P 06 achieved the highest PCA score (1.126) and entropy-weighted TOPSIS score (0.796). L.P 06 inhibited 59.02% of α-amylase activity, 95.33% of α-glucosidase activity, 77.71% of pancreatic lipase activity, and 89.86% of ACE. It scavenged 83.77% of 1,1-diphenyl-2-picrylhydrazyl radical and 83.02% of hydroxyl radical, and its total antioxidant capacity was 7.159 mmol/L. Furthermore, both L.P 06 and L.Pc 02 exhibited excellent probiotic properties, suggesting their potential for development as functional food ingredients. Combining entropy-weighted TOPSIS with PCA overcomes the limitations of their single use, enabling more accurate and efficient screening of functional LAB with the potential to prevent the “three high”. These results offer a new strategy for tackling these metabolic disorders and contribute to the development of novel functional lactic acid bacteria.