Mulholland's early research examined the oxidation of amino acids and nitrogen cycling by the marine bacteriumTrichodesmium. Her subsequent work investigated nitrogen cycling in harmful algae including Aureococcus and Karenia brevis. She has examined how phytoplankton will respond to an ocean enriched in carbon dioxide, the impact of climate change on the Chesapeake Bay, and the contribution of nitrogen-fixing organisms to nutrient cycling. Her research tracks organic compounds in seawater, for example cyanate or compounds produced by phytoplankton. In coastal environments she has researched the impact of coastal flooding and the movement of pollution during floods. As of 2022 she has an h-index of 46 and has publications that have been cited more than 7000 times.