During the last decade, autonomous residential photovoltaic (PV) systems have been widely installed, especially in remote areas (islands, rural territories, etc.), in an effort to produce electrical energy in a reliable and inexpensive manner. The appropriate design of a PV system and the compatibility of its power quality indices with national and international standards are crucial for efficient and economical autonomous operation of the system. To this direction, the critical parameters of a three-phase autonomous PV residential system are properly determined. Moreover, a new design methodology that meets the demanded standards and improves further the power quality is also introduced. Finally, an optimization algorithm is designed utilizing artificial intelligence techniques. The analytical results are corroborated by extensive simulation results and insightful discussions are provided demonstrating the efficiency of our proposed design.