The terrestrial flora around Padilla Bay, aside from the agricultural fields and diked areas, consists of second-growth forests of mixed conifers, broad leaf trees and occasional pastures. Forests are dominated primarily by Douglas-fir, western red cedar, red alder, Pacific madrone, and big leaf maple. The understory includes salal, Oregon grape, stinging nettle, Indian plum, and ocean spray. Shrimp and crab, especially the Dungeness crab, are of great economic importance. Taylor's sea slugs, ribbon worms, polychaete worms, lug worms, brooding anemone, jellyfish, and amphipods.
Herring are the bay's most economically-significant fish species.
Herring and smelt both use the bay's eelgrass beds for spawning. Common flat fish include English sole, Dover sole, rock sole and starry flounder. During the winter, the bay contains an average of 50,000 ducks of 26 species. A large colony of great blue heron live in a rookery on Samish Island. While their nesting area is outside the boundaries of the Reserve, they feed in both Samish and Padilla Bays.