Aim: The aim of this study was to evaluate and compare the side effects of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs)—ibuprofen, naproxen, diclofenac, and celecoxib—in the treatment of rheumatoid arthritis (RA), from a clinical pharmacology perspective. Materials and Methods: This study included 100 patients diagnosed with RA who were receiving NSAID treatment. The participants were selected from a tertiary care hospital, ensuring diverse demographic representation. The inclusion criteria required at least one month of NSAID therapy. Clinical evaluations, laboratory tests, and patient-reported outcome measures (PROMs) for pain intensity, functional disability, and quality of life were conducted over a 6-month period. Statistical analysis was used to evaluate adverse side effects, laboratory abnormalities, and PROMs. Results: The results indicated that gastrointestinal distress was the most common side effect, reported by 28.00% of ibuprofen users, 33.33% of naproxen users, and 40.00% of diclofenac users. Celecoxib had the lowest incidence at 20.00%. There were no significant differences between the NSAIDs regarding the frequency of side effects (p-values ranging from 0.245 to 0.782). Laboratory abnormalities, such as elevated liver enzymes, decreased renal function, and low hemoglobin levels, were rare and not significantly different across the NSAIDs. PROMs showed no significant differences in pain intensity, functional disability, or quality of life across the NSAIDs. Conclusion: This study found no significant differences in the side effects, laboratory abnormalities, or PROMs between ibuprofen, naproxen, diclofenac, and celecoxib in RA treatment. All four NSAIDs demonstrated similar safety profiles, with gastrointestinal distress being the most common side effect. These findings suggest that these NSAIDs are comparable in terms of both efficacy and safety in managing RA.