Weeds cause destructive agricultural losses, so weed control is an urgent challenge facing agriculture. The extensive use of synthetic chemical herbicides has detrimental environmental impacts and promotes the emergence of resistant species. Therefore, in this study we tried to find a new natural weed control that can ensure biosafety and eco-sustainability. The phytotoxic potential of culture filtrates of the endophytes Bacillus inaquosorum NL1 and Bacillus safensis NL2 isolated from Nerium oleander leaf against the invasive harmful weed species Cenchrus echinatus was evaluated. Culture filtrates of both bacterial species exhibited potent phytotoxic activity, which resulted in 100% germination inhibition of C. echinatus. The chemical analysis of culture filtrates revealed high contents of total phenolics and n-alkanes that have phytotoxic effects against seed germination. According to the findings of this study the endophytic bacteria associated with N. oleander leaf can be used in the future to develop a sustainable bio-herbicide formulation.