In the 21st century, Type 2 diabetes mellitus (T2DM) stands out as a critical metabolic condition, indicated by insulin deficiency and resistance stemming from various endogenous factors. The prevalence of T2DM is alarming, with projections indicating a surge from 366.2 million to 578 million cases by 2030 and an estimated 783 million individuals affected by 2045. In response to this global health challenge, extensive research has been directed towards identifying therapeutic targets to address T2DM. Numerous investigative efforts have focused on preserving the action of endogenous glucagon-like peptide (GLP)-1 by inhibiting the activity of Dipeptidyl peptidase IV (DPP IV). Additionally, the exploration of peroxisome proliferator-activated receptor (PPAR-γ) agonists, the activation of glycation end products, stimulation of Di acyl glycerol transferase kinase pathways (DGAT-I), utilization of Sodium glucose co-transporter 1 (SGLT-1) and SGLT-1 inhibitors, as well as the investigation of SIRT-1 agonists, have emerged as promising therapeutic avenues for managing T2DM. This review provides valuable insights into both current and novel targets in the pursuit of developing new drugs. These drugs, envisioned as potential monotherapies or components of combination therapies, hold the potential to function as dual-active agents in addressing the complexities of metabolic disorders. By understanding and leveraging these therapeutic targets, researchers and clinicians aim to develop innovative treatments that can significantly impact the management and mitigation of T2DM.