Diversification of farming systems at plot scale is increasingly seen as an essential option to meet agriculture sustainability challenges and support agroecological transition. Significant progress has been made in recent years on methods for designing diversified cropping systems based on annual crops. However, few methods have been tested for designing diversified cropping systems based on perennial crops, and in particular perennial crop-based agroforestry systems, despite their important dietary and economic roles in the world. In this study, we argue that the characteristics of perennial crops induce specific structural and functional changes that impact the design process. We identified four key concepts for the design of diversified perennial crop-based agroforestry systems: (i) the targeted productivity must be considered over the long term and at the plot level, and encompass not only the productive and non-productive stages of perennial crops but also of associated plants; (ii) these systems will eventually face shocks and crisis in their lifetime, so they should be designed with resilience and adaptability in mind; (iii) initial designs will necessarily evolve throughout the long lifespan of perennial crops, and so a combination of de novo design from scratch and step-by-step design approaches for regeneration or transformation will be required; and (iv) due to the high complexity of these systems and the difficulty of setting up trials, the design process should draw from a range of knowledges from academics and practitioners and hybrid them. These four key features show that perennial crops offer distinct opportunities for the design of sustainable diversified cropping systems, but also face specific challenges that require more transdisciplinary research.