Context: Depression is a common disease among human beings, and because of different factors the patients suffer from mental disorders and do not have healthy life. In Holy Quran, the word “grief” is mentioned as a synonym for depression, and also other words such as “sorrow”, “regret”, “anguish”, “distress” and “sadness” are indicated. From the viewpoint of Holy Quran, grief is divided into two types as praised and condemned, the condemned grief refers to depression, but the praised grief is necessary for excellence and development. In the Islamic lifestyle, which Holy Quran and behavior of Holy Prophet and his inmate are its basis, the emphasis on mental health and prevention of grief and sorrow are among its most important indicators and indexes. The current study aimed to prevent and treat depression, according to Islamic lifestyle. Evidence Acquisition: Holy Quran, narratives and behavior of inmate were evaluated to codify Quranic lifestyle, and provide prevention and treatment methods of depression, descriptively and analytically. Results: In the first step, Holy Quran helps people avoid depression and in this regard introduces factors such as “sincerity”, “resistance”, “virtue”, “trust in God”, “belief”, “good deeds” and etc. as grief protection factors. A bunch of Holy Quran verses, with precise and meticulous look, point to the causes of grief such as “punishment of sins in this world and the hereafter”, “financial and human loss”, “jealousy”, “failure” , “fear of the enemy”, and etc. Quran, this book of guidance, by dragging the attention of human to some epistemic-educative notes such as “divine aid”, “worship” , “prayer”, “ mercy of God”, “support of angels” and some other means introduces depression and grief removing factors. Conclusions: By analyzing and evaluating Quran verses and Islamic narratives, it is concluded that the grief is divided into two types as praised and condemned which praised grief is dedicated to righteous and God’s men and calmness, tranquility, increasing life expectancy are among the properties of this type of grief. According to religious texts, the condemned grief is a mental depression which usually affects individuals who cannot withstand hardships and challenges of life and lose their mental balance. This type of grief can be prevented and treated, according to the Quranic commands and following Quranic lifestyle.