AbstractParkinson's disease (PD) is one of the prevalent neurodegenerative diseases, and developing new treatments from natural products is of particular interest. Essential oils from Cinnamomum osmophloeum ct. linalool leaves contain high levels (~95%) of S‐(+)‐linalool. The neuroprotective effects of linalool have been previously described, yet the underlying molecular mechanisms remain largely unknown. This study aimed to investigate the potential anti‐Parkinsonian's effect of S‐(+)‐linalool on mitochondrial regulation and decipher the underlying molecular mechanisms in Caenorhabditis elegans PD model. Essential oils at 20 mg/L and 20 mg/L S‐(+)‐linalool each significantly attenuated the damaging effects of 6‐hydroxydopamine (6‐OHDA) on dopaminergic (DA) neurons and decreased the mitochondrial unfolded protein response (UPRmt) to antimycin. RNAi knockdown of mitochondrial complex I (gas‐1, nuo‐1), and complex II (mev‐1) genes prevented the improvement of mitochondrial activity by S‐(+)‐linalool. The protective effects of S‐(+)‐linalool on 6‐OHDA‐induced behavior changes were absent in a DA‐specific strain of C. elegans produced by gas‐1, nuo‐1, and mev‐1 RNAi knockdown. These results suggest the potential anti‐Parkinsonian's effect of S‐(+)‐linalool is associated with mitochondrial activity and regulated by gas‐1, nuo‐1, and mev‐1 in C. elegans. Our findings suggest that S‐(+)‐linalool might be a promising candidate for therapeutic application to inhibit the progression of PD.