The use of bioherbicides for the sustainable management of weeds is one of the main challenges of agriculture. With this approach, the application of complex (crude) extract has shown to be inore efficient and less expensive due to phytotoxic (together) presence, than single, isolated, or majority compounds. In this perspective, the aqueous extract of the five Piper spp. (Piper divaricatum, P. hispidum, P. marginatum, P. peltatum, and P. reticulatum) native from the Amazon region, Brazil were used to evaluate the physiological and oxidative effects on the emergence and growth of common weeds under controlled conditions and in greenhouse. The extract obtained in sufficient quantity and the expected inhibitory effect was used in biochemical assays again with lettuce (indicator plant) and weeds seedlings, focusing on antioxidative enzymes activity. We verify the allelopathic potential of the P. divaricatum and P. peltatum, which caused high toxicity to lettuce and weeds seedlings in vitro and in vivo assays. In both Piper extract at 1.5%, the emergence inhibition of weed seedlings was up to 70%. This concentration also influenced the growth of seedlings. As to responses of antioxidative enzymes, we found that lettuce seedlings were widely affected by the exposition of Piper extracts (P. divaricatum and P. peltatum) at 5%, with an input of 89%, 300%, and 290% on SOD, CAT, and APX activities, respectively. Thus, Piper divaricatum and P. peltatum are potent allelopathic species that could contribute to minimize the damage of crops caused by weed competitions.