At the beginning of is career, working at the Nizzoli Associati studio, he took part to the design of the Italsider factory in Taranto.
After ten years, dedicated to journalism in the Seventies, he started again to design with the Alchimia group, of which he becomes the main exponent. He re-designs objects, he takes for instance the classical design chairs and re-creates them using new colours and materials. He covered the Universale chair by Joe Colombo with faked marble finishes, and re-created the Wassily chair by Marcel Breuer with coloured and asymmetric inserts and the Superleggera chair by Gi� Ponti with signs.
He designed for Alchimia the Proust armchair, decorated with the pointillism technique, then manufactured by Cappellini in 1993, the Kandissi sofa, the Scivolando chair, some models of the series Il mobile infinito. He co-operates with international companies such as Philips, Swarovski, and he is artistic consultant to various Far East manufacturers providing direction for design and brand identity strategies. He contributed to the definition of the Swatch company design strategies, and created for them exclusive watches models (in 1990 the Cosmesis and the Metroscape watches).
Since 1983 he has been Design and Communications Director for Alessi. He has re-designed its whole production and introduced the corkscrew Anna G (1994). "Its name – Menini says -, has been proposed by Alberto Alessi, because its physiognomy reminded him of the famous designer Anna Gili, whom I deeply respect. Anna, after having thought about it, has agreed. This object is a sort of design portrait".
The corkscrew has had a big success. People love it for its loud colours, it is a solar object, alive, with its own personality, "it stares at you and makes you think of a dance, through its movement". In the following years, Anna G has acquired a number of new functions: the Anne Time kitchen timer, the Anne Candle candleholder, the Anne Pepper pepper-grinder, the Anne Cheese grater, the Anne Face pendant (2001). 
After all these female versions, Mendini created a male object: the Anna G corkscrew fellow, which he has named Sandro M., a sort of self-portrait next to a first lady. 
Afterwards he went back to exteriors architecture thank to Alberto Alessi, who had asked him to design his Casa della Felicit� (1983-1989) in Omegna. "Alberto, a close friend of mine – Mendini says in an interview on Rai Educational – told me: 'I would like you to design my home because you are not an architect'. I didn't get angry for this statement, as I considered it quite true. That house has been accurately designed. I've convinced other architects to work with me, Bob Venturi, Aldo Rossi, Ettore Sottsass, Achille Castiglioni, Andrea Branzi and others: it is a sort of patchwork. It has been my first approach to the field of architecture. A very intense experience".
Mendini also designed the Teatrino della Bicchieraia in Arezzo, the Alessi factories and Forum-Museum in Omegna, the renovation of part of the Termini Railway Station in Rome, a tower building in Hiroshima in Japan, the Groningen Museum in Holland, the Casin� Arosa in Arosa, a whole district in Lugano in Switzerland, two subway stations and the restoration of the City Hall in Naples.