Current global estimates suggest that more than 537 million young adults are living with diabetes worldwide, which has become a serious health burden. From the genetic perspective, diabetes falls into two categories, viz. monogenic and polygenic diabetes. The complexity of the diabetes architecture is of great stress to diagnostic and prognostic research. Next-generation sequencing (NGS), such as whole-genome and whole-exome sequencing approaches, have provided numerous new insights into the molecular bases of monogenic and polygenic type of diabetes. With the use of high-throughput sequencing technologies, more recent advancements have been observed in diabetes research in the past few years. The NGS helped in numerous ways, such as mapping the causal rare and common genetic variants, identifying the novel candidate genes, predicting the population-based disease epidemiology, the functional role of genes in disease etiology and pathogenesis, identifying pharmacogenomic targets for drug discovery and implications in precision and personalized diabetic therapy. The review highlights the importance of high-throughput sequencing technologies in the effective diagnostic capability and management of diabetes.