In this work, crude extracts of Niger seed hull (NSH) were used to conduct anti-leech (Limnatis nilotica) experimental activity. Following the standard method, the phytochemical screening of methanol and chloroform extracts was evaluated. The crude methanol extract contained secondary metabolites as terpenoids, flavonoids, and saponins. According to severity effects ranging from 4+ to 1+ and timing zones from 1 to 720 min, including negative paralysis, the paralyzing time was calculated. From 1+ to 4+ severities, the crude extract of NSH exhibited strong anti-leech action. Methanol and chloroform extracts exhibit anti-leech properties that are comparable to the reference medication levaminsole. The dosage contraction of NSH in all dose levels of the standard reference drug Lavamisole resulted in a considerable death of leeches, as shown by the first-order reaction (χ2 = 62.9, df = 5, p < 0.05). The methanol and chloroform extracts of NSH significantly differed in how many leeches they were able to kill (χ2 = 355, df = 5, p < 0.05 and χ2 = 711.7, df = 5, p < 0.05, respectively). Differential canning calorimetry (DSC) was used to characterize the stability research of NSH crude extracts. Thermogram results revealed that four principal chemicals were valid in the 49.5 °C to 300 °C temperature range. According to a pharmacokinetic model, methanolic-extracted NSH kills the leech parasite more quickly than chloroform-extracted NSH. The current kinetic parameter results imply that methanol extract NSH has better anti-leech activity, and that it is a time-saving and environmentally acceptable organic chemical for future relevance to prevent anti-leech activity, and might be chosen for further research.