This study aims to investigate the effect of curcumin (Cur) on glucose and oxygen deprivation/reoxygenation (OGD/R)-induced brain microglial cell BV2 injury by regulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. BV2 cells were separated into control group, OGD/R group, low-dose Cur group (4 μmol/L), medium-dose Cur group (8 μmol/L), high-dose Cur group (16 μmol/L), and high-dose Cur+JAK2 activator (10 μmol/L) group. CCK-8 method was applied to detect the proliferation of BV2 cells. Annexin V-FITC/PI was applied to detect cell apoptosis. The reactive oxygen species (ROS) detection kit was used to detect the generation of ROS in BV2 cells. Commercial kits were used to measure the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the levels of malondialdehyde (MDA) in BV2 cells ELISA was applied to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in BV2 cells. RT-qPCR was used to detect the mRNA levels of TNF-α, IL-1β, and IL-6 in BV2 cells. Western blot was applied to determine the expression levels of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and p-STAT3 proteins. The results showed that compared with the control group, the survival rate of BV2 cells, SOD activity, and GSH-Px activity in the OGD/R treatment group were lower (P<0.05), while the apoptosis rate, ROS generation, MDA level, TNF-α, IL-1β, IL-6 expression, and p-JAK2/JAK2, p-STAT3/STAT3 levels were higher (P<0.05). Compared with the OGD/R group, the survival rate of BV2 cells, SOD activity, and GSH-Px activity in the low, medium, and high-dose Cur groups were higher (P<0.05), while the apoptosis rate, ROS generation, MDA level, TNF-α, IL-1β, IL-6 expression, and p-JAK2/JAK2, p-STAT3/STAT3 levels were lower (P<0.05), showing a dose-dependent relationship (P<0.05). Compared with the high-dose Cur group, the survival rate of BV2 cells, SOD activity, and GSH-Px activity in the high-dose Cur+JAK2 activator group were lower (P<0.05), while the apoptosis rate, ROS generation, MDA level, TNF-α, IL-1β, IL-6 expression, and p-JAK2/JAK2, p-STAT3/STAT3 levels were higher (P<0.05). In conclusion, Cur may alleviate OGD/R-induced BV2 cell damage, promote cell proliferation, inhibit oxidative stress and inflammatory cytokine secretion by inhibiting JAK2/STAT3 signaling pathway activation.