Commercial fishing is common on the Damariscotta River. Species include softshell clams (Mya arenaria), oysters (Crassostrea virginica and Ostrea edulis), lobster (Homarus americanus), scallops (Placopecten magellanicus), menhaden (also known as pogies – Brevoortia tyrannus), alewives (Alosa pseudoharengus), and urchins (Strongylocentrotus droebachiensis ), among other species.

The Damariscotta River’s sea farms produce the majority of the state’s farmed oysters. Most farmers grow American oysters (Crassostrea virginica), although in the past, European oysters (Ostrea edulis). Both oyster species can be found in wild populations along the banks of the river. Other farmers grow blue mussels (Mytilus edulis) and kelp (primarily Saccharina latissima, Laminaria digitata, and Alaria esculenta), and are experimenting with sea scallops (Placopecten magellanicus).

Recreational fishing is also popular, with striped bass (Morone saxatilis) and mackerel (Scomber scombrus) being most common.

The Damariscotta River is also popular for tourism, recreation, and conservation. Many people kayak, paddleboard, boat, or swim on the river. Hiking and wildlife viewing from the shore is popular, as are guided kayaking or aquaculture farm tours. Multiple conservation groups are active in the area and protect land and provide public access to the outdoors in the region while working to improve and maintain forest and water quality.