More than 80,000 original artifacts are kept in the Sakhalin Regional Museum, in about ten departments. The stores of the museum have document, picture, and numismatic collections, and archaeological collections from such unique sites as Imchin and Kurilorussia.

The ethnographic collections attract special attention. They include both everyday and sacred articles made by the indigenous peoples of Sakhalin: Ainu, Nivkh and Orok. In 1948 B.A.Zherebtsov, the director of the museum, collected from the Ainu of South Sakhalin one of the oldest and rarest Ainu collections. It comprises 160 articles, including, among other things, wooden and varnished tableware, metal decorations for clothes, a bow and a quiver for arrows, a tobacco-pouch, and mouthpieces for pipes.

A palaeontological collection takes a special place among the natural history items. It includes fossils of plants and animals, unique samples of late Cretaceous ammonites, fossilized shells of Cephalopoda mollusks, notable for their high degree of preservation, mammoths' teeth and many specimens. The Museum stores have collections of Sakhalin rocks, minerals, semi-precious and artificial stones (among them Malokurilskii agates and amber from the eastern Sakhalin coast), herbariums and dried species of animals (mollusks, Crustacean, echinodermata, insects, fish, amphibians, reptiles, birds, mammals). Some of the natural scientific collections were made at the beginning of the 20th century. The collection of marine and sea and coast animals of Sakhalin and the Kurile Islands, together with typical land residents, has exotic species as well: a large blue butterfly (Papilio maackii) and a peacock butterfly Artemida (Actias artemis), a stag-beetle (Lucanus maculifemoratus), an Abalone shell (Haliotis sp.), two marine turtles, a Pacific Leatherback Turtle (Dermochelys criacea), and a Hawksbill Turtle (Eretmoshelys imbricata), and several other animals.

The Museum store of fine arts numbers about 500 articles of painting, drawing, sculpture and decorative applied art. The People's Republic of China presented a collection of art to the Sakhalin museum in the 1950s. This collection includes small nephrite sculptures, Chinese lanterns, metal and china vases, traditionally ornamented, silk embroideries, and many other items.