After the First World War, his work gained even greater momentum, increasing the number of schools, colleges and charitable works; at the same time that new needs were presenting themselves. For example, he created the “Little Cottolengos”, institutions dedicated to the education and promotion of the disabled or people with severe limitations (mental or physical conditions). Generally no one cared about these people. Their relatives used to abandon them on the streets or leave them on the outskirts of big cities in the hope that someone would pick them up. Through the Cottolengos Don Luis gave them a home, help and protection. The name of these assistance centers has its origin in the work started by San Giuseppe Benedetto Cottolengo, creator of the first ‘little houses’ for the disabled.
Don Orione, on the other hand, promoted the construction of the sanctuaries of the Virgin of the Guard in Tortona and of the Virgin of Caravaggio in Funo.
The saint also managed to send missionary expeditions to various parts of the world, in which he himself participated. These missions were carried out to Latin American countries such as Argentina, Brazil, Uruguay and Chile.
Don Luis enjoyed the esteem of Popes Saint Pius X, Benedict XV, Pius XI and Pius XII. Due to his people skills, kindness and intelligence, the aforementioned pontiffs, at different times, would entrust him with various specific tasks – diplomatic missions, conflict resolution, pastoral visits, etc. – inside and outside the Church, over decades.