The museum's collection houses 27,000 items that represent the uniqueness and distinctiveness of the Krāslava region from ancient times to the present. Among them are archaeological objects, a large collection of ethnographic items, documents, photographs, valuable 18th-19th century books, and other collections, which are regularly displayed in the museum's thematic exhibitions.

The museum’s art collection includes over 1,000 works of fine art, including pieces by artists such as Pāvils Glaudāns, Vanda Zēvalde, Vitālijs Kalvāns, Jāzeps Pīgožņs, Osvalds Zvejsalnieks, Inta and Kārlis Dobrāji, Pēteris Postažs, Valda Mežbārde, Leonīds Bauliņš, Valentīns Zlidņs, Daiga Lapsa, Nadīna Lavrecka, and other artists.

In the museum's exhibition hall, a new art exhibition is presented every two months. Krāslava artists' exhibitions have become a tradition at the museum. Visitors can also explore thematic historical exhibitions.