Scotland-born lock George Biagi comes into the starting XV, along with flanker Maxime Mbanda, hooker Ornel Gega and centre Tommaso Benvenuti.
Dries van Schalkwyk and Leonardo Ghiraldini drop to the bench.
And the injured Michele Campagnaro and Glasgow Warriors flanker Simone Favaro do not feature in the squad.
Replacement Federico Ruzza could win his first senior cap.
Italy have lost all of their matches so far in this year's championship, while Scotland have two wins from four.
However, the Azzurri won on their last visit to Murrayfield, beating the Scots 22-19 in 2015.
E Padovani (Zebre), A Esposito (Treviso), T Benvenuti (Treviso), L McLean (Treviso), G Venditti (Zebre), C Canna (Zebre), E Gori (Treviso); A Lovotti (Zebre), O Gega (Treviso), L Cittadini (Bayonne), M Fuser (Treviso), G Biagi (Zebre), M Mbanda (Zebre), A Steyn (Treviso), S Parisse (Stade Francais, capt).
Replacements: L Ghiraldini (Toulouse), S Panico (Calvisano), D Chistolini (Zebre), D van Schalkwyk (Zebre), F Ruzza (Zebre), F Minto (Treviso), M Violi (Zebre), L Sperandio (Treviso).
Italy head coach Conor O'Shea has made four changes to his side to face Scotland in the final round of this year's Six Nations.