The real-time application of piezoelectric nanogenerators (PNGs) under a harsh environment remains a challenge due to lower output performance and poor durability. Thus, the development of flexible, sensitive, and stable PNGs became a topic of interest to capture different human motions including gesture monitoring to speech recognition. Herein, a scalable approach is adapted where naphthylamine bridging a [Cd(II)-μ-I4] two-dimensional (2D) metal-organic framework (MOF)-reinforced poly(vinylidene fluoride) (PVDF) composite nanofibers mat is prepared to fabricate a flexible and sensitive composite piezoelectric nanogenerator (C-PNG). The needle-shaped MOF was successfully synthesized by the layering and diffusion of two different solutions. The incorporation of single-crystalline 2D MOF ensures a large content of electroactive phases (98%) with a resultant high-magnitude piezoelectric coefficient of 41 pC/N in a composite nanofibers mat due to the interfacial specific interaction with -CH2-/-CF2- dipoles of PVDF. As an outcome, C-PNG generates high electrical output (open-circuit voltage of 22 V and maximum power density of 24 μW/cm2) with a very fast response time (tr ≈ 5 ms) under periodic pressure imparting stimuli. Benefiting from bending and twisting functionality, C-PNG is capable of scavenging biomechanical energy by mimicking complex musculoskeletal motions that broaden its application in wearable electronics and fabric integrated medical devices. In addition, C-PNG also demonstrates an efficient acoustic vibration to electric energy conversion capability with an improved power density and acoustic sensitivity of 6.25 μW and 0.95 V/Pa, respectively. The overall energy conversion efficiency is sufficient to operate several consumer electronics without any energy storage unit. This acoustic observation is further validated by the finite element method-based theoretical simulation. Overall, the 2D MOF-based device design strategy opens up a new possibility to develop a human-motion compatible energy generator and a self-powered acoustic sensor to power up electronic gadgets as well as low-frequency noise detection.