Today's industrialized agriculture and food production systems rely heavily on input-based land use. Among the inputs, pesticides are one of the main issue regarding human health and the environment. However, nature- and biodiversity-based strategies to avoid the use of synthetic chemicals through e.g. natural pest regulation, are proposed and are a necessary part of an agroecological transition. In a project launched in Switzerland, a catalogue of agroecological measures inspired by organic agriculture, including preventive and alternative practices for natural pest control (pathogens, pests, weeds), such as cover crops, intercropping, flower strips and biological control agents is being implemented in a network of 67 farms. The implementation follows a process of co-innovation involving farmers, scientists and extension services, so that pesticide application is minimized but allowed in case of predictable high yield lost. After three main crops over three years of implementation the lessons learned so far show that it is difficult to achieve the goal of sustainable production systems that combine a 75% reduction in pesticide use with a yield reduction of less than 10%. Benefits for biodiversity in general can be shown but involvement of farmers is of crucial importance, and therefore, biodiversity-based functions such as natural pest regulation act as an important lever to promote biodiversity as a whole.