Microplastic (MP) pollution represents a critical challenge for global water quality due to its persistence, ubiquity, and ecotoxicological impacts. While conventional coagulation/flocculation–sedimentation (CFS) processes using chemical coagulants are partially effective, they often entail high energy demands, toxic residuals, and environmental trade-offs. This article provides a comprehensive and up-to-date review of recent advances in the use of natural coagulants (NCs) derived from plant, animal, and microbial sources as sustainable alternatives for MP removal from aquatic systems. The novelty of this work lies in its integrative analysis of bio-coagulant performance with hybrid formulations, nano-enhanced composites, and process intensification strategies such as enzyme activation. Through critical synthesis of various peer-reviewed studies published between 2020 and 2025, the review highlights that NCs such as Moringa oleifera, chitosan, Cactus mucilage, and microbial EPS can achieve MP removal efficiencies exceeding 90% under optimized conditions, with significantly reduced sludge toxicity and carbon footprint. Furthermore, the review identifies key performance parameters; pH, ionic strength, NOM interference, and coagulant modification techniques that influence the physicochemical mechanisms driving MP-coagulant interactions, including charge neutralization, bridging flocculation, hydrophobic association, and bio-adhesion. Pilot-scale evaluations demonstrate the feasibility of hybrid systems (e.g., chitosan-FeCl₃, Moringa–alum) in achieving near-complete removal (up to 99.8%) of MPs across a range of polymer types and sizes. However, critical limitations remain, such as variability in raw material composition, reduced efficiency for MPs <10 μm, and scalability constraints. The study concludes that although NCs cannot yet fully replace synthetic ones at scale, their use as coagulant aids or in hybrid systems shows promise for sustainable water treatment. Future research should focus on standardizing extraction methods, improving bioengineering for higher protein yields, and developing smart coagulation systems for adaptive control across various water matrices.