Tectoridin is one of the most active components extracted from flowers of P. lobate and has a variety of activities including antioxidative and anti-inflammatory activities. The functions and potential mechanisms underlying Tectoridin in cerebral ischemia/reperfusion (I/R) injury have not been well interpreted. This study was carried out from the neuroprotection of the nervous system. 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay served for evaluating the neurological deficit score as well as measuring the brain infarct size. HE staining served for examining the brain tissue pathological change. Measurement of the superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) and the malondialdehyde (MDA) level was also carried out. Moreover, the expressions of PI3K/AKT/mTOR, TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathway related proteins were measured by Western blot. The results showed that, relative to the sham group, the Tectoridin group could more remarkably prevent neurological deficit, manifested as decreased brain infarct volume. Besides, the Tectoridin treatment assisted in decreasing the inflammation level by reducing MDA level significantly and the enhanced GSH–Px level and SOD activity significantly, thereby leading to the brain damage reduction. In addition, Tectoridin led to the activation of the protective antioxidative Nrf2/HO-1 pathway. Tectoridin exerted protective effect by suppressing the expression of TLR4, MYD88 and NF-κB, which were two pivotal inflammatory mediators. At last, Tectoridin hindered apoptosis based on the up-regulation of p-AKT, Bcl-2/Bax and p-mTOR expressions. This research preliminarily revealed the mechanism of Tectoridin in the treatment of ischemic stroke and provided support for the further application of Tectoridin.