New Perspectives on the Old Uses of Traditional Medicinal and Edible Herbs: Extract and Spent Material of Persicaria hydropiper (L.) Delarbre

<b>Background/Objectives:</b><i>Persicaria hydropiper</i> (L.) Delarbre, commonly known as water pepper, possesses multifunctional potential. Our research focuses on its complex phenolic composition, bioactivity, safety evaluation and utilization in a sustainable manner. Moreover, a survey was conducted among the Serbian population to gain insight into the attitude towards traditional wild-growing herbs (i.e., <i>P. hydropiper</i>), the level of familiarity with their zero-waste culture, and to assess eating behaviors. <b>Methods:</b> A survey was conducted with 168 participants to assess attitudes towards traditional herbs, zero-waste culture, and eating behaviors, while cytotoxicity, in vivo toxicity, chemical analysis of secondary metabolites, and probiotic viability assays were performed to evaluate the effects of the PH extract. <b>Results:</b> Notably, <i>P. hydropiper</i> extract (PH) exhibits a diverse phenolic profile, including quinic acid (3.68 ± 0.37 mg/g DW), gallic acid (1.16 ± 0.10 mg/g DW), quercetin (2.34 ± 0.70 mg/g DW) and kaempferol-3-<i>O</i>-glucoside (4.18 ± 0.17 mg/g DW). These bioactive compounds have been linked to anticancer effects. The tested extract demonstrated a cytotoxic effect on the human neuroblastoma cell line, opening questions for the further exploration of its mechanisms for potential therapeutic applications. Based on the toxicity assessment in the <i>Artemia salina</i> model, the PH could be characterized with good safety, especially for the lower concentrations (LC₅₀ = 0.83 mg/mL, 24 h). The utilization of the spent PH material supports the viability of psychobiotic strains (up to 9.26 ± 0.54 log CFU/mL). Based on the conducted survey, 63.7% (<i>n</i> = 107) of respondents mainly prefer traditional instead of imported herbs. The respondents were skeptical about zero-waste edibles; 51.2% (<i>n</i> = 86) would not try them, and a bit more than half were not familiar with zero-waste culture (57.7%; <i>n</i> = 97). Only 8.3% (<i>n</i> = 14) followed a flexitarian diet as a dietary pattern. <b>Conclusions:</b> The use of underutilized traditional plants and their spent material could potentially contribute to the acceptance of a zero-waste culture in Serbia. Reinventing the use of neglected traditional plants and addressing ways for spent material valorization could contribute to the acceptance of a zero-waste strategy and encourage healthier eating behavior.