Exploring plant rodenticide is of great importance, as rodent damage has become a major ecological and environmental problem of many countries all over the world. The study was performed to elucidate the rodenticidal activity of acetonic, methanolic, and mixture of both extracts of Heliotropium curassavicum on adult male albino rats as alternatives to conventional rodenticides. The toxic effects of Heliotropium curassavicum acetonic, methanolic, and a mixture of both extracts at doses (625 and 825 mg/kg b.wt.), were evaluated compared to the toxicity of zinc phosphide (5 mg/kg b.wt.) under laboratory conditions, as well as control groups (tween 80, vegetable oil and distilled water) all administered by oral gavage for 28 days. Results showed a significant elevation in Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and alkaline phosphates (ALP) serum levels as affected by all tested treatments compared to control groups. On the other hand, a significant decline in α, β- Acetylcholinesterase (AchE), and Gamma-Aminobutyric Acid (GABA) levels was detected. Furthermore, there is a significant rise in the extent of micronucleus cell production in bone marrow smears of the treated rats compared to the control groups. Also, DNA fragmentation was noticed in hepatic and brain tissues after treatment with curassavicum plant extracts and zinc phosphide. Histopathological findings showed obvious perturbations in the liver and brain tissues that proved the previously mentioned results. Generally, our data reinforced that using the mixture of both extracts triggered more toxic impacts and rodenticidal activities than using each extract individually and could serve as a safer alternative of zinc phosphide.