AbstractSchisandra chinensisis a medicinal plant used to treat various diseases. Extracts from the leaves or fruits ofS. chinensisand their components are used in osteoarthritis (OA). The OA inhibitory effect of schisandrol A, one of its components, has been previously confirmed. We aimed to confirm the OA inhibitory effect ofSchisandra(including components like schisandrol A) to identify why the inhibitory effect of theSchisandraextract is better. First, we investigated the effects of theSchisandraextract on OA as a potential therapeutic. Experimental OA was induced in a mouse model via destabilized medial meniscus surgery. The animals were orally administered theSchisandraextract; the inhibition of cartilage destruction was confirmed using histological analysis. In vitro analysis showed that theSchisandraextract attenuated osteoarthritic cartilage destruction by regulating IL‐1β‐induced MMP3 and COX‐2 levels. TheSchisandraextract inhibited IL‐1β‐induced degradation of IκB (NF‐κB pathway) and IL‐1β‐induced phosphorylation of p38 and JNK (mitogen‐activated protein kinase (MAPK) pathway). RNA‐sequencing analysis showed that theSchisandraextract decreased the expression of IL‐1β‐induced MAPK and NF‐κB signalling pathway‐related genes more than schisandrol A alone. Therefore,Schisandraextract may be more effective than schisandrol A in preventing OA progression by regulating MAPK and NF‐κB signalling.