Osteoarthritis (OA) is the most common form of arthritis and affects millions of people worldwide. Patients have traditionally been treated with non-steroidal anti-inflammatory drugs (NSAIDs), but these are associated with significant side effects. Purification of the acetone extract of Alpinia galanga afforded p-hydroxycinnamaldehyde, as identified by nuclear magnetic resonance and mass spectrometry analyses. By exploiting the cartilage explant culture, p-hydroxycinnamaldehyde suppressed loss of uronic acid, resulting in release of hyaluronan (HA), sulfated glycosaminoglycans (s-GAGs) and matrix metalloproteinases (MMPs). p-Hydroxycinnamaldehyde and interleukin-1beta (IL-1beta), when incubated in primary human chondrocytes, also reduced release of HA, s-GAG and MMP-2. The results demonstrated: (a) that expression levels of the catabolic genes MMP-3 and MMP-13 were suppressed and (b) mRNA expression levels of anabolic genes of collagen II, SOX9 and aggrecan were increased. This study shows that p-hydroxycinnaldehyde from A. galanga Linn. is a potential therapeutic agent for treatment of OA.