The pathophysiology of osteoarthritis (OA) involves the destruction of articular cartilage and the overgrowth of bone with lipping and spur formation. Nerve endings in the joint capsule and adjacent tissues play a major role in the pain mechanisms of osteoarthritis. This often requires patients to seek pain control measures beyond over-the-counter drugs, such as local anesthetics. Osteopathic manipulation treatment (OMT) is a conservative, non-pharmacological treatment that can be used to help treat chronic pain associated with OA. Other non-pharmacologic therapies include weight loss, exercise, physical therapy (PT), and assistive devices. However, pharmacologic management may be added synergistically to control flares and maintain baseline activities of daily living. While oral non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay of treatment for pain and inflammation associated with OA, they have a non-selective inhibitory action that often results in negative side effects when used chronically. The possibility of minimizing these complications through alternate treatments such as topical NSAIDs provides an opportunity for patients to receive adequate pain relief from OA without suffering unnecessary consequences. This literature review seeks to assess the state of research regarding topical NSAIDs and OMT as alternatives to the current gold-standard treatment of OA. The significant inclusion criteria consisted of articles that described the effects of OMT on OA or the use of topical NSAIDs such as Voltaren on OA. Due to the limited articles found, a qualitative analysis was performed, and the salient conclusions are outlined. Alternative pharmacological and non-pharmacological treatments, such as topical diclofenac gel and OMT, have shown promising results in the treatment of pain in OA. It is seen that a majority of patients achieve pain management using NSAIDs, acetaminophen, or topical analgesics. Both diclofenac sodium and OMT have individually been shown to be effective treatments of OA when compared to the use of oral NSAIDs. A holistic treatment approach that utilizes both topical diclofenac sodium and OMT may provide OA patients with an effective option to reduce their moderate to severe chronic pain with limited side effects. Further, high-quality randomized controlled trials are needed to identify whether synergistic effects occur when combining diclofenac sodium gel and OMT for pain relief in patients with OA.