Summary: Nonlinearities, such as dead-zone, backlash, hysteresis, and saturation, are common in the mechanical and mechatronic systems’ components and actuators. Hence, an effective control strategy should take into account such nonlinearities which, if unaccounted for, may cause serious response problems and might even result in system failure. Input saturation is one of the most common nonlinearities in practical control systems. So, this article introduces a novel adaptive variable structure control strategy for nonlinear Caputo fractional-order systems despite the saturating inputs. Owing to the complex nature of the fractional-order systems and lack of proper identification strategies for such systems, this research focuses on the canonic systems with complete unknown dynamics and even those with model uncertainties and external noise. Using mathematical stability theory and adaptive control strategy, a simple stable integral sliding mode control is proposed. The controller will be shown to be effective against actuator saturation as well as unknown characteristics and system uncertainties. Finally, two case studies, including a mechatronic device, are considered to illustrate the effectiveness and practicality of the proposed controller in the applications.