Mechanical sensing and transduction are integral to biological systems and have inspired research into the regulation of supramolecular self-assembly via mechanical forces. This review presents an inaugural discussion on mechanically active supramolecular systems. It focuses on two primary mechanisms for modulating these systems: the incorporation of mechanophores and the application of mechanical forces to modulate non-covalent interactions. Challenging the traditional view of mechanical forces as solely destructive, their constructive potential when harnessed through sophisticated design is showcased. Investigation is done on how external forces like ultrasound, stirring, vortex, tension, and compression can induce fluorescence in π-conjugated systems, initiate hydrogelation, propel non-equilibrium self-assembly, and affect the structure of vesicles. The review also casts light on the prospective uses of mechanically active supramolecular systems in areas such as protein activation, drug delivery, and stress sensing, illustrating the nuanced role of mechanical forces as both disruptors and enablers in the creation of functional materials.