Photoplethysmography (PPG) is an optical technique with high diagnostic potential, yet clinical applications remain underdeveloped. Standardization of signal recording and quantification of waveform are essential prerequisites for broader clinical use. The aim of this study was to utilize a two-stage multi-Gaussian fitting technique in order to examine the parameters of conduit artery PPG waveform recorded during increasing the unilateral regional vascular resistance (RVR). This study was conducted on 14 young and healthy volunteers; various external compressions (ECs) were performed by inflating a tight cuff at 0, 40, 80, and 200 mmHg, while registering femoral PPG (wavelength 880 nm), diameter, blood flow linear velocity (vascular ultrasound), and the arterial pressure (Finapres) during the states of the baseline, partial, and total arterial occlusion, and resultant reactive hyperemia. An increase of the EC elevated the arterial stiffness (AS) and the unilateral distal RVR, and caused a shift of the fitted multi-Gaussian parameters: a decreased delay between reflected and traverse wave components and an increased ratio of their amplitudes. It was concluded that two-stage multi-Gaussian waveform quantification demonstrates an approach potentially extending the use of arterial site PPG in the assessment of diagnostically useful markers e.g., the RVR and the AS.