Smartphone-based technologies for medical imaging purposes are limited, especially when it involves the measurement of physiological information of the tissues. Herein, a smartphone-based near-infrared (NIR) imaging device was developed to measure physiological changes in tissues across a wide area and without contact. A custom attachment containing multiple multi-wavelength LED light sources (690, 800, and 840 nm; and <4 mW of optical power per LED), source driver, and optical filters and lenses was clipped onto a smartphone that served as the detector during data acquisition. The ability of the device to measure physiological changes was validated via occlusion studies on control subjects. Noise removal techniques using singular value decomposition algorithms effectively removed surface noise and distinctly differentiated the physiological changes in response to occlusion. In the long term, the developed smartphone-based NIR imaging device with capabilities to capture physiological changes will be a great low-cost alternative for clinicians and eventually for patients with chronic ulcers and bed sores, and/or in pre-screening for potential ulcers in diabetic subjects.