Osteoarthritis (OA) is a prevalent chronic articular deteriorating disease that is defined by subchondral bone lesions, inflammation, immunology in the synovium, and deterioration of articular cartilage. Globally, the condition affects 2–6% of people, and its frequency increases to nearly 40% in those over the age of 70. Although it can affect any joint, the knee, hands, hip, and spine are the joints that are frequently affected. At the moment, pharmacological treatments for cartilage disease have not been able to fully regenerate the affected tissue that contributed to the joint’s functional loss. A different course of treatment includes using several types of nonsteroidal anti-inflammatory drugs (NSAIDs) at the specified dosages. However, these NSAIDs have small benefits and major adverse effects. In this sense, we need to think about new therapeutic alternatives based on different natural compounds to delay osteoarthritis progression and regulation of articular homeostasis. Recently, increasing interest has been devoted to the treatment of osteoarthritis by some probiotics, herbal medicines, etc. For the fact that different bioactive compounds act as cartilage protective, anti-inflammatory, or antioxidants, daily consumption of the probiotics Lactobacillus casei Shirota for 6 months exhibited beneficial effects on knee osteoarthritis. There are some antagonizing pro-inflammatory bacterial species like Bifidobacterium, which can act with prebiotics to give protection against degeneration of the joints. Among different herbal sources, ginger has great active constituents which possess similar functions to synthetic drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). Ginger acts as an anti-inflammatory by downregulating progesterone production like a nonsteroidal anti-inflammatory drug. Honey also has several potent bioactive compounds, such as chrysin, apigenin, flavonoids, and phenolic compounds; these are potential regulators of articular homeostasis in osteoarthritis. There is a piece of clear evidence that bioactive molecules from different biological sources will be promising candidates for the treatment of osteoarthritis.