Chronic obstructive pulmonary disease (COPD) has become one of the most fatal diseases of the century considering mortality and morbidity levels worldwide. This disease is an inflammatory response to environmental stress and tobacco smoking. Although spirometry is the gold-standard diagnostic test administrated in primary and secondary care, it often exhibits low accuracy in cases of predicting disease worsening and possible bias due to the operator, patient, and conditions. Recent developments in proteomics research suggest that the presence of protein biomarkers can aid in the accurate diagnosis and prediction of disease outcomes. This review presents the cutting-edge research progress in the area of protein biomarkers towards the management of COPD. The literature review was confined to protein biomarkers in saliva and sputum because testing these bodily fluids shows great promise for point-of-care (POC) testing due to its practicality, non-invasiveness and inexpensive handling and sampling. Although it is conclusive that more studies on sputum and saliva are needed, this review studies the promising clinical value of interleukin (IL)-6 and IL-8, matrix metalloproteinase (MMP)-8 and MMP-9, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and neutrophil elastase (NE). Following the critical analysis of salivary and sputum biomarkers, the recent development of POC biosensors for the multiplexed detection of biomarkers is also reported. Overall, the review aims to explore the possibility for the future development of POC sensors for chronic lung disease management utilizing clinically relevant biomarkers in saliva and sputum.