The inhibitory reagents to inhibit the activation of microglial cells may be potentially useful for the treatment of neurodegenerative diseases. The leaves of the plant Laurus nobilis belonging to the family Lauraceae, namely, bay leaves, have been used as a popular spice, and their extract showed moderate inhibition on microglial activation. A further phytochemical investigation of the leaves led to the isolation of two new (1, 2) and eight known (3-10) sesquiterpenes. Their structures were elucidated on the basis of extensive 1D and 2D NMR (HMQC, HMBC, (1)H-(1)H COSY, and NOESY) spectroscopic data analyses and Chem3D modeling. The following biological studies disclosed that these isolated compounds showed inhibitory activities on LPS-induced microglial activation. The results of our phytochemical investigation, including two new sesquiterpenes (1 and 2) and the first report of two compounds (3 and 4) from this species, further revealed the chemical composition of bay leaves as a popular spice, and the biological studies implied that bay leaves, containing bioactive substances with the inhibition of microglial activation, were potentially beneficial to human health.