Low-grade gliomas (LGGs) are a heterogeneous group of tumors with an average 10-year survival rate of 40-55%. Current treatment options include chemotherapy, radiotherapy, and gross total resection (GTR) of the tumor. The extent of resection (EOR) plays an important role in improving surgical outcomes. However, the major obstacle in treating low-grade gliomas is their diffused nature and the presence of residual cancer cells at the tumor margins post resection. Cold Atmospheric Plasma (CAP) has shown to be effective in targeted killing of tumor cells in various glioma cell lines without affecting non-tumor cells through Reactive Oxygen and Nitrogen Species (RONS). However, no study on the effectiveness of CAP has been carried out in LGG tissues till date. In this study, we applied helium-based CAP on tumor tissues resected from LGG patients. Our results show that CAP is effective in promoting RONS accumulation in LGG tissues when CAP jet parameters are set at 4kV voltage, 5min treatment time and 3lpm gas flow rate. We also observed that CAP jet is more effective in thinner slice preparations of tumor as compared to thick tumor samples. Our results indicate that CAP could prove to be an effective adjunct therapy in glioma surgery to target residual cancer cells to improve surgical outcome of patients with low-grade glioma.