After spending his youth development years at Saint-Étienne he was signed by Liverpool's manager Gérard Houllier in August 2003. Liverpool beat off stiff competition from Premiership rivals Arsenal, Manchester United and German giants Bayern Munich to secure his services. In an interview with L'Equipe, Medjani revealed he left Saint-Étienne because he was willing to stay if given an opportunity with the first team but his request was turned down by Manager Frédéric Antonetti.
Medjani then struggled to break in Liverpool first team so he was sent on loan to Lorient for the whole 2004–05 season by new Liverpool manager Rafael Benítez, where he made twenty five appearance. Despite impressing in the Toulon under-20 tournament in summer 2005, Benítez deemed it necessary for him to gain more experience and so he spent 2005–06 on loan at Metz.
At the start of the 2006–07 season, he rejoined Lorient, this time on a permanent basis.
In the 2007–08 season, Medjani moved down to Ligue 2 joining Ajaccio for the remainder of the season.
The 2008–09 season earned Medjani a permanent move with the club on a three-year deal. Medjani soon made an immediate impact when he scored his first goal in the second round of Coupe de la Ligue during Ajaccio's 4–2 loss against Montpellier. On 20 February 2009, Medjani came on as a substitute in the second half and 18 minutes to the game, Medjani was sent off, along with Brahim Ferradj in the same minute, as Ajaccio drew 1–1 with Brest. Medjani scored his first league goal of the season during Ajaccio's 3–1 defeat to Strasbourg.
Following the 2009–10 season and the World Cup, Medjani was linked with Ligue 2 side Nantes. Ajaccio finished as runners-up in Ligue 2 resulting in their promotion to Ligue 1. Medjani signed a two-year contract extension until 2013. In the 2011–12 season, Medjani continued to be in the first team, either playing in centre back and defensive midfield. Medjani scored his first goal in a 3–1 loss against Paris Saint-Germain on 16 October 2011. On 10 December 2012, Medjani made a mistake in the final minutes, allowing Daniel Niculae to score in a 2–2 draw against Nancy, in a match which could have ended Ajaccio thirteen games without winning. In April, Medjani scored his second goal of the season, in a 1–1 draw against Saint-Étienne.
Ahead of the 2012–13 season, Medjani expressed his desire to leave the club. In December, Medjani started to wear the captain's armband.
In January 2013, just prior to the closing of the transfer window, Medjani joined Monaco on a three and a half year contract from Ajaccio.
Following Monaco promotion, Medjani was told by Manager Claudio Ranieri that his first team would be limited following the club's spending spree.
In July 2013, Medjani was sent out on loan to Olympiacos from Monaco until 1 January 2014, with the option of a permanent move. After six months with few appearances at Olympiacos, he returned to his parent club.
Upon his return to France, Monaco then loaned him out to Valenciennes till the end of 2013/14 season.
Following his loan spell at Valenciennes, Medjani’s time at Monaco came to an end despite having two years of his contract left.
After leaving Monaco, Medjani was linked with a move to Trabzonspor and Cagliari Calcio before joining Trabzobspor on a three-year contract. He scored his first goal for the club in the play-off round of the Europa League as Trabzonspor beat Rostov 2–0 in the first leg.
On 30 January 2016 La Liga side Levante UD have signed Medjani until the end of the season, with an option to extend the contract for another season. On 25 July, after suffering relegation, he signed a one-year contract with CD Leganés also in the main category. On 9 January 2017, Medjani rescinded with Lega and signed with Trabzonspor again.
Medjani has an Algerian father and a French mother, and was eligible for both national teams. Medjani captained the France U21 team in the 2006 Toulon tournament. However, being of Algerian origin, he made the switch to represent Algeria in international competitions and was called up by Rabah Saâdane to the Algerian preliminary squad for the 2010 FIFA World Cup.Scores and results list Algeria's goal tally first.
While growing up, Medjani revered boxer Muhammad Ali.