Background: Pes anserine syndrome is characterized by pain in the proximal medial tibial region, commonly associated with knee osteoarthritis (OA) due to its bursal sac inflammation. The usual course of treatment for pes anserine syndrome is supportive, ranging from physiotherapy to NSAIDs, with steroid injections for refractory cases. It was reported that the use of dextrose 5% in water (D5W) has shown promise in treating chronic musculoskeletal conditions without the adverse effects associated with steroids. Objective: This study evaluates the efficacy of ultrasound-guided D5W and lidocaine injections in treating pes anserine syndrome in knee OA patients. Study Design: This study is conducted towards three patients with pes anserine syndrome and knee OA. Material and Methods: Three patients with pes anserine syndrome and knee OA received ultrasound-guided injections of a mixed 2cc D5W and 1cc lidocaine in a 3cc syringe guided by the ultrasound into the fascias between the pes anserine muscles. Pain was evaluated using the VAS five days later. Results: All patients reported significant pain reduction of 25-75%, along with improvements in daily activities. Discussion: The role of D5W injections in pain relief is presumably linked with various mechanisms. In this study, lidocaine provided immediate pain relief, while D5W sustained its effects by stabilizing neural activity, normalizing regional glucose metabolism, and reducing neurogenic inflammation. Conclusion: D5W injections proved a promising result to replace steroids in treating pes anserine syndrome, although further studies are needed to confirm efficacy and optimize treatment protocols.