Ischemic stroke is a cerebral hemodynamic disorder that occurs due to the impairment of hemoglobin supply to the tissue, a leading cause of mortality around the world. This research focuses on detecting ischemic stroke conditions by adding new hemodynamic biomarker information to the proposed low-cost wearable point-of-care diagnostic near-infrared spectroscopy (NIRS) device. Consequently, a new protocol-based sequence of experiments has been carried out to detect the ischemic condition. First, a multichannel, multiwavelength, and multibiomarkers-based point-of-care NIRS system has been developed to accommodate these features onboard. A four-wavelength, six-optode channels-based NIRS probe has been designed such that the physiological noise gets minimized and covers 100 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times20$ </tex-math></inline-formula> mm area of tissue, for example, the frontal lobe of the brain, with near and far distance concept of optode channels. Infinite impulse response (IIR) filters have been used onboard to improve the signal-to-noise ratio (SNR) up to 58.17 dB of the measured biomarker signal. The proposed pipeline of in-vivo occlusion experimentation evoked the ischemic condition at various stages to validate the system performance and temporal characteristics of biomarkers. First, basic PPG signals have recorded to test the performance of the device against the standard PPG signal, then the device has been placed a little upward from the finger to the forearm, where forearm occlusion has been done to mimic the ischemic condition, and finally, the device has been moved further upward and placed at the frontal lobe to record the evoked ischemic biomarker’s response while blocking the carotid artery.