To counteract host plant defenses, aphids secrete salivary effectors during feeding. Exact functional roles of many salivary effectors in Sitobion avenae (Fabricius), are still elusive. Here, we cloned a salivary glutathione peroxidase (GPx) coding gene (i.e., SaE23) in S. avenae. Our bioinformatics analyses indicated that SaE23 might originate from gene duplication events. Overexpression of SaE23 inhibited Bax-triggered programmed cell death and flg22-elicited reactive oxygen species bursts. The expression patterns showed that SaE23 was predominantly expressed in salivary glands, and its expression increased significantly upon feeding on the resistant wheat cultivar Z4WM. Knockdown of SaE23 significantly reduced aphid survival rates on Z4WM, compared with the susceptible wheat cultivar AK58. Feeding of SaE23 silenced-S. avenae triggered upregulation of TaLOX2 in jasmonic acid pathway, TaICS2 and TaPR-1 in salicylic acid pathway, three MYB transcription factors (TaMYB19, TaMYB29 and TaMYB44) and TaGLS2 for callose synthase genes, which might contribute to decrease performance of SaE23-silenced individuals. Our results showed that SaE23 could be a novel molecular target for management of S. avenae, providing insights into the potential origin of GPx in aphids and molecular mechanisms of GPx modulating aphid-plant interactions.