Schistosomiasis ranks among the greatest threats to global public health. Elucidating the infectivity of Schistosoma mansoni, one of human schistosomiasis’s common etiological agents, requires improved understanding of the behavioural mechanisms of cercariae, the non-feeding mammalian infective stage. This study investigated the presence and effect of cercariae neuropeptides on their behaviour when applied externally. Cercariae were peptidomically analysed and gene ontology enrichment and KEGG pathway analyses were performed with reference to the S. mansoni genome. Eleven novel neuropeptide precursor proteins specific to the cercariae stage and Schistosoma genus were identified. The protein-protein interaction analysis displayed that FLLALPSP-OH, NRKIDQSFYSYY-NH2 and YIRF-NH2 neuropeptide precursor proteins interacted with each other with strong similarities to neural activity-related proteins. Behavioural bioassays were performed using eight putative neuropeptides at 3 mg/mL. FLLALPSP-OH significantly decreased the velocity of cercariae active states, while NRKIDQSFYSYY-NH2 decreased velocity and increased the frequency of angular change in active states. NRKIDQSFYSYY-NH2 retained its bioactivity at 0.1 mg/mL and over a duration of 6 hr. In contrast, YIRF-NH2 did not produce significant changes in cercariae behaviour despite structural similarities to FMRF-related neuropeptides in other digenetic trematodes. These findings identify behavioural-altering novel neuropeptides which may inform future biocontrol innovations to prevent infection and minimise human schistosomiasis.