Plant-derived antifertility agents have been investigated for decades as potential contraceptives for both women and men. Interest has intensified as health systems seek additional nonhormonal options, culturally acceptable methods, and low-cost technologies—while recognizing that contraceptive development must meet strict standards of safety, reversibility, effectiveness, and user acceptability. Plant research offers multi-target biochemical mechanisms: modulation of the hypothalamic–pituitary–gonadal axis, disruption of spermatogenesis or sperm function, inhibition of ovulation, alteration of endometrial receptivity, or local spermicidal effects. However, the field also faces persistent constraints: heterogeneous evidence quality, limited standardization of complex extracts, incomplete compound identification, variable reversibility, and safety concerns. Historical experience with gossypol illustrates both potential and risk—high efficacy but toxicity and incomplete recovery in some users (Qian, 1984; Liu et al., 1987; Liu, 1987; Coutinho, 1988). More recent work on triptonide from Tripterygium wilfordii suggests a promising nonhormonal male contraceptive mechanism with reversibility in animal models (Chang et al., 2021), and neem has been reviewed as a multipurpose plant with contraceptive potential (Patil et al., 2021). This article provides a framework synthesis (≤2024) that maps plant antifertility mechanisms, summarizes representative evidence across male and female approaches, and proposes a staged roadmap for translation. Results are presented as two conceptual figures (reproductive targets and evidence ladder) and three tables addressing (1) target–assay alignment, (2) challenges with mitigation strategies, and (3) opportunity pathways and institutional actions. We conclude that plant antifertility research can contribute to future contraceptive innovation if it shifts from isolated screening toward standardized, mechanism-aligned, reversible, and ethically governed evidence programs with transparent safety evaluation and partnership-ready translational planning.