Traditional rice (Oryza sativa L.) management (tillage and flooding) is unsustainable due to soil degradation and the large amount of irrigation water used, an issue which is exacerbated in the Mediterranean region. Therefore, there is a need to explore rice management strategies in order to improve water-use efficiency and ensure its sustainability. Thus, field experiments were conducted to determine the medium-term effects of different irrigation and tillage methods combined with a single compost application on water and rice productivity, as well as food safety in a semiarid Mediterranean region. The management systems evaluated were: sprinkler irrigation in combination with no-tillage (SNT), sprinkler irrigation in combination with conventional tillage (ST), which were implemented in 2015, and flooding irrigation in combination with conventional tillage (FT), and their homologues (SNT-C, ST-C, and FT-C) with single compost application in 2015. In reference to rice grain yield, the highest values were observed under ST treatment with 10 307 and 11 625 kg ha−1 in 2018 and 2019 respectively; whereas between FT and SNT there were no significant differences, with 8 140 kg ha−1 as mean value through the study. Nevertheless, sprinkler irrigation allowed saving 55% of the total amount of water applied in reference to flooding irrigation. Furthermore, the highest arsenic concentration in grains was found under FT but it decreased with compost application (FT-C) and especially with sprinkler irrigation, regardless of tillage management systems. However, sprinkler irrigation favors the cadmium uptake by plants, although this process was reduced under SNT in reference to ST, and especially under amended compost treatments. Therefore, our results suggested that a combination of sprinkler irrigation and compost application, regardless of the tillage system, could be an excellent strategy for rice management for the Mediterranean environment in terms of water and crop productivity as well as food safety.