<p>Nickel (Ni) is an essential micronutrient and plays an important role in various physiological and biochemical processes in plants. However, high Ni levels can have multiple detrimental impacts on plant growth, crop productivity, food quality, and ultimately human health. To address this challenge, plants have evolved a complex network of mechanisms to regulate Ni uptake, transport, distribution, and detoxification, which can be leveraged for effective Ni mitigation strategies in crop production. This review highlights the complex interactions of Ni absorption, retention, and transport within plant tissues and its impact on the physio-biochemical processes of plants. While describing the negative effects of Ni toxicity on crop growth and yield, the risks to human health from consuming Ni-contaminated agricultural products are also explained. This thorough literature review also discusses the network of different mechanisms for tolerating and detoxifying Ni accumulation in plants. This review also covers a wide range of advanced strategies for Ni-induced stress mitigation in crops, such as agronomic practices, soil amendments, crop treatments, and genetically engineered approaches. It also emphasizes the significance of Ni toxicity to plant health, food safety, and sustainability, pointing out future research regarding Ni remediation.</p> Graphical abstract <p></p>