In our modern lifestyle, the cocktail of organic pollutants from everyday items, such as hair dyes, cloth dyes, food colours, hair oils, cooking oils, and agricultural proteins, enters water streams through household pipelines. This unnoticed contamination, growing alarmingly, poses a serious challenge beyond the scope of conventional separation techniques, calling for a comprehensive solution. While membrane technology offers a promising solution, it grapples with persistent surface fouling issues. This study introduces a novel approach through the development of extraordinary Polyvinylidene fluoride-Montmorillonite-Cucurbit[6]uril (PVDF-M-CB[6]) mixed matrix membranes, presenting a potential breakthrough in overcoming surface fouling challenges and offering a versatile solution for the separation of an array of organic contaminants. Powered by the synergistic host–guest supramolecular complexation of CB[6] onto montmorillonite (M) clay support, these membranes demonstrate swift and selective encapsulation, leading to superior cationic dye rejection. Adding to the allure, CB[6]’s structure encourages favorable carbonyl interactions with bovine serum albumin (BSA), effectively repelling the protein away from the membrane, while also promoting seamless oil–water emulsion separation with an underwater oil contact angle of 150 ± 3°, displaying its superoleophobic nature and enhancing remarkable antifouling properties. The PV-M-CB[6] membranes showcased 2x removal of cationic dyes, 1.3x removal of anionic dyes, 1.4x oil–water emulsion separation, and 2x BSA separation compared to the pristine polyvinylidene fluoride (PVDF) membrane. These membranes displayed 98.3 % efficiency in oil–water emulsion separation and sustained a flux recovery ratio of over >75% after seven cycles. Overall, PV-M-CB[6] membranes represent an innovative solution with heightened hydrophilicity, remarkable antifouling performance, and exceptional proficiency in delivering one-stop organic foulant separation.