The pollution of the natural environment and particularly the world’s oceans by plastic litter is a significant concern. In recent years, macro and microplastics have been found in various environmental compartments such as freshwater and seawater, but also in the atmosphere, sediments, soils, sewage sludge, biota, and ultimately in human food. As a result of sun exposure (ultraviolet radiation) and mechanical agitation like the continuous force of waves, microplastics can further degrade into even smaller particles in the sub-micron range, the nanoplastics. The increasing presence of micro- and nanoplastics (MNPs) is raising great scientific and societal concern due to the potential effects they can have on wildlife and ecosystems. They can also affect human health, mainly when these materials bioaccumulate and magnify in the food chain. The latest efforts by the European Commission (EC) to reduce the amount of plastic released into the aquatic environments were undertaken within the framework of the European Green Deal, the Circular Economy Action Plan, and the Zero Pollution Action Plan to restrict the sale of microplastics and products to which they are intentionally added. Besides this legal measure, several solutions have proposed global programs, and especially actions promoted by the EC as alternatives to mitigate the problem of plastic and microplastic pollution. These comprise the creation of taxes applicable to plastic, the development of better technologies for recycling, or the promotion and encouragement of the reuse, reduction and substitution of these materials. Concerning the last point, the development of bio-based polymeric materials has been one of the most promising alternatives. The emergence of bio-based plastics presents opportunities to reduce the amount of hazard plastic litter. However, there is also a need to ensure that bio-based plastics can be safer options considering safety and sustainability from early stages in the value chain to guarantee booth human and environmental health, as intended by the Chemical Strategy for Sustainability (CSS) and the SSbD Framework. There has been limited systematic research on the fate of bio-based plastics in the environment and their potential effects on organisms and ecosystems. In the case of marine environments, there is a lack of reliable testing methods and standards for assessing and certifying negative impacts, such as toxic effects, bioaccumulation, or their capability to act as vectors of pathogens. Integrated or new approaches to assess the potential effects of bioplastics in aquatic environments should consider studies at different levels, including bioassays with specific organisms from freshwater or seawater. Mesocosm studies are a valuable complement, as they offer more realistic ecological conditions than laboratory tests. They allow studying of the behavior and effects of pollutants by assessing higher-level biological variables (e.g., community) and study species interactions and indirect effects.