The flower of Hibiscus syriacus Linn is a well-known traditional Chinese medicine (TCM) and health food in China, which has been used to treat dysentery, vaginal discharge, and hemorrhoids. In this study, five polyphenols (compounds 1–5) and five fatty acids (compounds 6–10) were isolated from the ethanol extract of the flower of H. syriacus. The isolated compounds were characterized by spectroscopic techniques. Polyphenols, an important type of natural product, have variety of biological activities. Here, we employed LPS or H2O2-treated SH-SY5Y cell models to test the neuroprotective effect of compounds 1–10. Results found compounds 1–5 (concentration range was around 20 μM on LPS model, concentration range was around 13 μM on H2O2 model), not compounds 6–10, exhibited neuroprotective effect in LPS or H2O2-treated SH-SY5Y cell. PCR analysis showed that compounds 1–5 can effectively improve the mRNA expression of synapse-related gene and neurotrophic factors (Syp, NGF and BDNF) in LPS-treated SH-SY5Y cell. In addition, compounds 1–5 decreased the levels of ROS and MDA and increased the activities of SOD, GSH-Px and CAT in LPS-treated SH-SY5Y cell. Furthermore, compounds 1–5 inhibited neuroinflammation (TNF-α, IL-1β and IL-6) in LPS-treated SH-SY5Y cell. In conclusion, the polyphenols in the flower of H. syriacus could be a promising candidate for preventive effect of neuroinflammation. © 2020 The Authors