As state senator, Padilla voted to support employment protections for medical cannabis patients and opposed DEA raids on cannabis companies. Padilla has expressed support for the federal MORE Act.
In 2021, Padilla filed an amendment that would allow veterans to access medical cannabis through the VA system in states where it is legal and require the VA to research the potential therapeutic benefits of cannabis for certain conditions.
In May 2022, Padilla joined a bipartisan effort requesting that congressional leadership include the Secure and Fair Enforcement (SAFE) Banking Act of 2021, which would allow state-legal cannabis business to access banking services, in the final version of competitiveness legislation currently being negotiated between the House and Senate.