Eichhornia crassipes were evaluated in order to investigate the insecticidal activity towards Aphis craccivora adults. The LC50 values were promising and reflected the bio-efficacy of the tested extracts (39 and 42 mg/L), respectively, and reduced the fecundity markedly. Using GC/MS analysis, the major components were n-hexadecanoic, linolenic, hexadecenoic, myristic, stearic acids, linole-laidic acid, methyl ester and some terpenoids, alkaloids, and hydrocarbons. A safety assessment of non-target organisms is essential for the development of new pesticides. In order to guide the rational use of the most potential insecticidal extracts AcF and EtF, the effect of these extracts on body weight, hematological indices, biochemical indicators, and histopathology of some relevant organs of albino rats (as a model for mammals) was investigated. The research outcomes revealed that the LC50 of AcF and EtF extracts had gradually raised body weight for 14 days (p > 0.05). Similarly, there were no remarkable alternations in the complete blood count (CBC); only a slight decrease in the monocytes count (612 ± 159.80 × 103 µL) in the EtF-treated group. There was a notable increase in alanine transferase (ALT) activity (36.73 ± 1.44 IU/L) in the AcF-treated group. No destructive changes were noted with the remaining biochemical parameters. Cholesterol and triglycerides non-significantly increased in the EtF group, whereas, cholesterol levels decreased significantly in the AcF group. In addition, histopathological examination reflected minor changes in AcF and EtF groups in the form of mild inflammation in the lungs and mild vacuolar degeneration in the kidneys, while no lesions were detected in the heart and liver in the same groups. Thus, the present research suggested that AcF and EtF extracts of E. crassipes are safe green insecticides for insect control strategies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.