COVID-19 pandemic presents an unprecedented challenge to identify effective drugs for treatment. Despite multiple clinical trials using different agents, there is still a lack of specific treatment for COVID-19. Having the possible role in suppressing inflammation, immune modulation, antiviral and improving respiratory symptoms, this review discusses the potential role of methylxanthine drugs like pentoxifylline and caffeine in the management of COVID-19 patients. COVID-19 pathogenesis for clinical features like severe pneumonia, acute lung injury (ALI) / acute respiratory distress syndrome (ARDS), and multi-organ failures are excessive inflammation, oxidation, and cytokine storm by the exaggerated immune response. Drugs like pentoxifylline have already shown improvement of the symptoms of ARDS and caffeine has been in clinical use for decades to treat apnea of prematurity (AOP) in preterm infants and improve respiratory function. Both pentoxifylline and caffeine are well-known anti-inflammatory and anti-oxidative molecules that have already shown to suppress Tumor Necrosis Factor (TNF-α) as well as other inflammatory cytokines in pulmonary diseases, and this may be beneficial for better clinical outcomes in COVID-19 patients. Pentoxifylline enhances blood flow, improves microcirculation and tissue oxygenation, and caffeine also efficiently improves microcirculation, reduces cardiovascular disease, and an effective analgesic. There are significant shreds of evidence that proved the properties of pentoxifylline and caffeine against virus-related diseases as well. Along with the aforementioned evidences and high safety profiles, both pentoxifylline and caffeine offer a glimpse of considerations for future use as a potential adjuvant to COVID-19 treatment. However, additional clinical studies are required to confirm this speculation.