Abstract Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.